Editorial

3 pages, 217 KiB

Open AccessEditorial

Regulatory Roles of Non-Coding RNAs in Cancer

by Macrina B. Silva-Cázares, Carlos Pérez-Plasencia and César López-Camarillo

Cells 2023, 12(9), 1298; https://doi.org/10.3390/cells12091298 - 02 May 2023

Viewed by 1111

For several decades, scientific research in cancer biology has focused mainly on the involvement of protein-coding genes [...] Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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12 pages, 3590 KiB

Open AccessCommunication

Bioinformatic miRNA-mRNAs Analysis Revels to miR-934 as a Potential Regulator of the Epithelial–Mesenchymal Transition in Triple-Negative Breast Cancer

by Jorge Alberto Contreras-Rodríguez, Jonathan Puente-Rivera, Diana Margarita Córdova-Esparza, Stephanie I. Nuñez-Olvera and Macrina Beatriz Silva-Cázares

Cells 2023, 12(6), 834; https://doi.org/10.3390/cells12060834 - 08 Mar 2023

Cited by 1 | Viewed by 1519

Abstract

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer and has the worst prognosis. In patients with TNBC tumors, the tumor cells have been reported to have mesenchymal features, which help them migrate and invade. Various studies on [...] Read more.

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer and has the worst prognosis. In patients with TNBC tumors, the tumor cells have been reported to have mesenchymal features, which help them migrate and invade. Various studies on cancer have revealed the importance of microRNAs (miRNAs) in different biological processes of the cell in that aberrations, in their expression, lead to alterations and deregulations in said processes, giving rise to tumor progression and aggression. In the present work, we determined the miRNAs that are deregulated in the epithelial–mesenchymal transition process in breast cancer. We discovered that 25 miRNAs that regulate mesenchymal genes are overexpressed in patients with TNBC. We found that miRNA targets modulate different processes and pathways, such as apoptosis, FoxO signaling pathways, and Hippo. We also found that the expression level of miR-934 is specific to the molecular subtype of the triple-negative breast cancer and modulates a set of related epithelial–mesenchymal genes. We determined that miR-934 inhibition in TNBC cell lines inhibits the migratory abilities of tumor cells. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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16 pages, 1814 KiB

Open AccessArticle

Using Single-Cell RNA Sequencing and MicroRNA Targeting Data to Improve Colorectal Cancer Survival Prediction

by Andrew Willems, Nicholas Panchy and Tian Hong

Cells 2023, 12(2), 228; https://doi.org/10.3390/cells12020228 - 05 Jan 2023

Cited by 4 | Viewed by 2439

Abstract

Colorectal cancer has proven to be difficult to treat as it is the second leading cause of cancer death for both men and women worldwide. Recent work has shown the importance of microRNA (miRNA) in the progression and metastasis of colorectal cancer. Here, [...] Read more.

Colorectal cancer has proven to be difficult to treat as it is the second leading cause of cancer death for both men and women worldwide. Recent work has shown the importance of microRNA (miRNA) in the progression and metastasis of colorectal cancer. Here, we develop a metric based on miRNA-gene target interactions, previously validated to be associated with colorectal cancer. We use this metric with a regularized Cox model to produce a small set of top-performing genes related to colon cancer. We show that using the miRNA metric and a Cox model led to a meaningful improvement in colon cancer survival prediction and correct patient risk stratification. We show that our approach outperforms existing methods and that the top genes identified by our process are implicated in NOTCH3 signaling and general metabolism pathways, which are essential to colon cancer progression. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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19 pages, 4334 KiB

Open AccessArticle

Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis

by Pengcheng Zhang, Mallory I. Frederick and Ilka U. Heinemann

Cells 2022, 11(23), 3742; https://doi.org/10.3390/cells11233742 - 23 Nov 2022

Cited by 2 | Viewed by 2082

Abstract

The terminal nucleotidyltransferases TUT4 and TUT7 (TUT4/7) regulate miRNA and mRNA stability by 3′ end uridylation. In humans, TUT4/7 polyuridylates both mRNA and pre-miRNA, leading to degradation by the U-specific exonuclease DIS3L2. We investigate the role of uridylation-dependent decay in maintaining the transcriptome [...] Read more.

The terminal nucleotidyltransferases TUT4 and TUT7 (TUT4/7) regulate miRNA and mRNA stability by 3′ end uridylation. In humans, TUT4/7 polyuridylates both mRNA and pre-miRNA, leading to degradation by the U-specific exonuclease DIS3L2. We investigate the role of uridylation-dependent decay in maintaining the transcriptome by transcriptionally profiling TUT4/7 deleted cells. We found that while the disruption of TUT4/7 expression increases the abundance of a variety of miRNAs, the let-7 family of miRNAs is the most impacted. Eight let-7 family miRNAs were increased in abundance in TUT4/7 deleted cells, and many let-7 mRNA targets are decreased in abundance. The mRNAs with increased abundance in the deletion strain are potential direct targets of TUT4/7, with transcripts coding for proteins involved in cellular stress response, rRNA processing, ribonucleoprotein complex biogenesis, cell–cell signaling, and regulation of metabolic processes most affected in the TUT4/7 knockout cells. We found that TUT4/7 indirectly control oncogenic signaling via the miRNA let-7a, which regulates AKT phosphorylation status. Finally, we find that, similar to fission yeast, the disruption of uridylation-dependent decay leads to major rearrangements of the transcriptome and reduces cell proliferation and adhesion. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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22 pages, 5296 KiB

Open AccessArticle

Breast Cancer Cells Reprogram the Oncogenic lncRNAs/mRNAs Coexpression Networks in Three-Dimensional Microenvironment

by Stephanie I. Nuñez-Olvera, Lorena Aguilar-Arnal, Mireya Cisneros-Villanueva, Alfredo Hidalgo-Miranda, Laurence A. Marchat, Yarely M. Salinas-Vera, Rosalio Ramos-Payán, Carlos Pérez-Plasencia, Ángeles Carlos-Reyes, Jonathan Puente-Rivera and Cesar López-Camarillo

Cells 2022, 11(21), 3458; https://doi.org/10.3390/cells11213458 - 01 Nov 2022

Cited by 3 | Viewed by 2197

Abstract

Organotypic three-dimensional (3D) cell cultures more accurately mimic the characteristics of solid tumors in vivo in comparison with traditional two-dimensional (2D) monolayer cell models. Currently, studies on the regulation of long non-coding RNAs (lncRNAs) have not been explored in breast cancer cells cultured [...] Read more.

Organotypic three-dimensional (3D) cell cultures more accurately mimic the characteristics of solid tumors in vivo in comparison with traditional two-dimensional (2D) monolayer cell models. Currently, studies on the regulation of long non-coding RNAs (lncRNAs) have not been explored in breast cancer cells cultured in 3D microenvironments. In the present research, we studied the expression and potential roles of lncRNAs in estrogen receptor-positive luminal B subtype BT-474 breast cancer cells grown over extracellular matrix proteins-enriched 3D cultures. Global expression profiling using DNA microarrays identifies 290 upregulated and 183 downregulated lncRNAs in 3D cultures relative to 2D condition. Using a co-expression analysis approach of lncRNAs and mRNAs pairs expressed in the same experimental conditions, we identify hundreds of regulatory axes modulating genes involved in cancer hallmarks, such as responses to estrogens, cell proliferation, hypoxia, apical junctions, and resistance to endocrine therapy. In addition, we identified 102 lncRNAs/mRNA correlations in 3D cultures, which were similar to those reported in TCGA datasets obtained from luminal B breast cancer patients. Interestingly, we also found a set of mRNAs transcripts co-expressed with LINC00847 and CTD-2566J3.1 lncRNAs, which were predictors of pathologic complete response and overall survival. Finally, both LINC00847 and CTD -2566J3.1 were co-expressed with essential genes for cancer genetic dependencies, such as FOXA1 y GINS2. Our experimental and predictive findings show that co-expressed lncRNAs/mRNAs pairs exhibit a high degree of similarity with those found in luminal B breast cancer patients, suggesting that they could be adequate pre-clinical tools to identify not only biomarkers related to endocrine therapy response and PCR, but to understand the biological behavior of cancer cells in 3D microenvironments. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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16 pages, 3151 KiB

Open AccessArticle

MEG3 Expression Indicates Lymph Node Metastasis and Presence of Cancer-Associated Fibroblasts in Papillary Thyroid Cancer

by Sina Dadafarin, Tomás C. Rodríguez, Michelle A. Carnazza, Raj K. Tiwari, Augustine Moscatello and Jan Geliebter

Cells 2022, 11(19), 3181; https://doi.org/10.3390/cells11193181 - 10 Oct 2022

Cited by 4 | Viewed by 2437

Abstract

Papillary thyroid cancer is the most common endocrine malignancy, occurring at an incidence rate of 12.9 per 100,000 in the US adult population. While the overall 10-year survival of PTC nears 95%, the presence of lymph node metastasis (LNM) or capsular invasion indicates [...] Read more.

Papillary thyroid cancer is the most common endocrine malignancy, occurring at an incidence rate of 12.9 per 100,000 in the US adult population. While the overall 10-year survival of PTC nears 95%, the presence of lymph node metastasis (LNM) or capsular invasion indicates the need for extensive neck dissection with possible adjuvant radioactive iodine therapy. While imaging modalities such as ultrasound and CT are currently in use for the detection of suspicious cervical lymph nodes, their sensitivities for tumor-positive nodes are low. Therefore, advancements in preoperative detection of LNM may optimize the surgical and medical management of patients with thyroid cancer. To this end, we analyzed bulk RNA-sequencing datasets to identify candidate markers highly predictive of LNM. We identified MEG3, a long-noncoding RNA previously described as a tumor suppressor when expressed in malignant cells, as highly associated with LNM tissue. Furthermore, the expression of MEG3 was highly predictive of tumor infiltration with cancer-associated fibroblasts, and single-cell RNA-sequencing data revealed the expression of MEG3 was isolated to cancer-associated fibroblasts (CAFs) in the most aggressive form of thyroid cancers. Our findings suggest that MEG3 expression, specifically in CAFs, is highly associated with LNM and may be a driver of aggressive disease. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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27 pages, 3287 KiB

Open AccessArticle

MiR-22 Deficiency Fosters Hepatocellular Carcinoma Development in Fatty Liver

by Monika Gjorgjieva, Anne-Sophie Ay, Marta Correia de Sousa, Etienne Delangre, Dobrochna Dolicka, Cyril Sobolewski, Christine Maeder, Margot Fournier, Christine Sempoux and Michelangelo Foti

Cells 2022, 11(18), 2860; https://doi.org/10.3390/cells11182860 - 14 Sep 2022

Cited by 2 | Viewed by 2461

Abstract

MiR-22 is mostly considered as a hepatic tumor-suppressor microRNA based on in vitro analyses. Yet, whether miR-22 exerts a tumor-suppressive function in the liver has not been investigated in vivo. Herein, in silico analyses of miR-22 expression were performed in hepatocellular carcinomas from [...] Read more.

MiR-22 is mostly considered as a hepatic tumor-suppressor microRNA based on in vitro analyses. Yet, whether miR-22 exerts a tumor-suppressive function in the liver has not been investigated in vivo. Herein, in silico analyses of miR-22 expression were performed in hepatocellular carcinomas from human patient cohorts and different mouse models. Diethylnitrosamine-induced hepatocellular carcinomas were then investigated in lean and diet-induced obese miR-22-deficient mice. The proteome of liver tissues from miR-22-deficient mice prior to hepatocellular carcinoma development was further analyzed to uncover miR-22 regulated factors that impact hepatocarcinogenesis with miR-22 deficiency. MiR-22 downregulation was consistently observed in hepatocellular carcinomas from all human cohorts and mouse models investigated. The time of appearance of the first tumors was decreased and the number of tumoral foci induced by diethylnitrosamine was significantly increased by miR-22-deficiency in vivo, two features which were further drastically exacerbated with diet-induced obesity. At the molecular level, we provide evidence that the loss of miR-22 significantly affects the energetic metabolism and mitochondrial functions of hepatocytes, and the expression of tumor-promoting factors such as thrombospondin-1. Our study demonstrates that miR-22 acts as a hepatic tumor suppressor in vivo by restraining pro-carcinogenic metabolic deregulations through pleiotropic mechanisms and the overexpression of relevant oncogenes. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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24 pages, 5009 KiB

Open AccessArticle

miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

by Patricia de la Cruz-Ojeda, Tobias Schmid, Loreto Boix, Manuela Moreno, Víctor Sapena, Juan M. Praena-Fernández, Francisco J. Castell, Juan Manuel Falcón-Pérez, María Reig, Bernhard Brüne, Miguel A. Gómez-Bravo, Álvaro Giráldez, Jordi Bruix, María T. Ferrer and Jordi Muntané

Cells 2022, 11(17), 2673; https://doi.org/10.3390/cells11172673 - 28 Aug 2022

Cited by 11 | Viewed by 3064

Abstract

Background: Sorafenib constitutes a suitable treatment alternative for patients with advanced hepatocellular carcinoma (HCC) in whom atezolizumab + bevacizumab therapy is contraindicated. The aim of the study was the identification of a miRNA signature in liquid biopsy related to sorafenib response. Methods: miRNAs [...] Read more.

Background: Sorafenib constitutes a suitable treatment alternative for patients with advanced hepatocellular carcinoma (HCC) in whom atezolizumab + bevacizumab therapy is contraindicated. The aim of the study was the identification of a miRNA signature in liquid biopsy related to sorafenib response. Methods: miRNAs were profiled in hepatoblastoma HepG2 cells and tested in animal models, extracellular vesicles (EVs), and plasma from HCC patients. Results: Sorafenib altered the expression of 11 miRNAs in HepG2 cells. miR-200c-3p and miR-27a-3p exerted an anti-tumoral activity by decreasing cell migration and invasion, whereas miR-122-5p, miR-148b-3p, miR-194-5p, miR-222-5p, and miR-512-3p exerted pro-tumoral properties by increasing cell proliferation, migration, or invasion, or decreasing apoptosis. Sorafenib induced a change in EVs population with an increased number of larger EVs, and promoted an accumulation of miR-27a-3p, miR-122-5p, miR-148b-3p, miR-193b-3p, miR-194-5p, miR-200c-3p, and miR-375 into exosomes. In HCC patients, circulating miR-200c-3p baseline levels were associated with increased survival, whereas high levels of miR-222-5p and miR-512-3p after 1 month of sorafenib treatment were related to poor prognosis. The RNA sequencing revealed that miR-200c-3p was related to the regulation of cell growth and death, whereas miR-222-5p and miR-512-3p were related to metabolic control. Conclusions: The study showed that Sorafenib regulates a specific miRNA signature in which miR-200c-3p, miR-222-5p, and miR-512-3p bear prognostic value and contribute to treatment response. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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13 pages, 1100 KiB

Open AccessArticle

Repetitive Sequence Transcription in Breast Cancer

by Walter Arancio and Claudia Coronnello

Cells 2022, 11(16), 2522; https://doi.org/10.3390/cells11162522 - 14 Aug 2022

Cited by 2 | Viewed by 2154

Abstract

Repetitive sequences represent about half of the human genome. They are actively transcribed and play a role during development and in epigenetic regulation. The altered activity of repetitive sequences can lead to genomic instability and they can contribute to the establishment or the [...] Read more.

Repetitive sequences represent about half of the human genome. They are actively transcribed and play a role during development and in epigenetic regulation. The altered activity of repetitive sequences can lead to genomic instability and they can contribute to the establishment or the progression of degenerative diseases and cancer transformation. In this work, we analyzed the expression profiles of DNA repetitive sequences in the breast cancer specimens of the HMUCC cohort. Satellite expression is generally upregulated in breast cancers, with specific families upregulated per histotype: in HER2-enriched cancers, they are the human satellite II (HSATII), in luminal A and B, they are part of the ALR family and in triple-negative, they are part of SAR and GSAT families, together with a perturbation in the transcription from endogenous retroviruses and their LTR sequences. We report that the background expression of repetitive sequences in healthy tissues of cancer patients differs from the tissues of non-cancerous controls. To conclude, peculiar patterns of expression of repetitive sequences are reported in each specimen, especially in the case of transcripts arising from satellite repeats. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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19 pages, 4063 KiB

Open AccessArticle

The Influence of MicroRNA-31 on Oxidative Stress and Radiosensitivity in Pancreatic Ductal Adenocarcinoma

by Jason McGrath, Laura E. Kane and Stephen G. Maher

Cells 2022, 11(15), 2294; https://doi.org/10.3390/cells11152294 - 25 Jul 2022

Cited by 7 | Viewed by 2364

Abstract

Radioresistance remains a significant challenge in treating pancreatic ductal adenocarcinoma (PDAC), contributing to the poor survival rates of this cancer. MicroRNAs (miRs) are small non-coding RNA molecules that may play an essential role in regulating radioresistance by altering the levels of oxidative stress. [...] Read more.

Radioresistance remains a significant challenge in treating pancreatic ductal adenocarcinoma (PDAC), contributing to the poor survival rates of this cancer. MicroRNAs (miRs) are small non-coding RNA molecules that may play an essential role in regulating radioresistance by altering the levels of oxidative stress. In this study, we investigated the role and potential mechanisms linking miR-31 to PDAC radioresistance. A pCMV-miR vector containing a miR-31 mimic was stably expressed into a miR-31-deficient PDAC cell line, BxPC-3. Additionally, a pmiRZip lentivector suppressing miR-31 was stably expressed in a miR-31 abundant PDAC cell line, Panc-1. Clonogenic assays were conducted to explore the role of miR-31 manipulation on radiosensitivity. Fluorometric ROS assays were performed to quantify ROS levels. The expression of potential miR-31 targets was measured by Western blot analysis. It was found that the manipulation of miR-31 altered the radiosensitivity in PDAC cells by regulating oxidative stress. Using online bioinformatics tools, we identified the 3′UTR of GPx8 as a predicted target of miR-31. Our study demonstrates, for the first time, that manipulating miR-31 alters GPx8 expression, regulating ROS detoxification and promoting either a radioresistant or radiosensitive phenotype. MiR-31 may represent a promising therapeutic target for altering radiosensitivity in PDAC cells. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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10 pages, 719 KiB

Open AccessArticle

Methylation Status of Gene Bodies of Selected microRNA Genes Associated with Neoplastic Transformation in Equine Sarcoids

by Klaudia Pawlina-Tyszko, Ewelina Semik-Gurgul, Tomasz Ząbek and Maciej Witkowski

Cells 2022, 11(12), 1917; https://doi.org/10.3390/cells11121917 - 14 Jun 2022

Cited by 2 | Viewed by 1584

Abstract

Horses are of great importance in recreation, livestock production, as working animals in poorly developed countries, and for equine-assisted therapy. Equine sarcoids belong to the most commonly diagnosed tumors in this species. They may cause discomfort, pain, and can lead to the permanent [...] Read more.

Horses are of great importance in recreation, livestock production, as working animals in poorly developed countries, and for equine-assisted therapy. Equine sarcoids belong to the most commonly diagnosed tumors in this species. They may cause discomfort, pain, and can lead to the permanent impairment of motor function. The molecular bases of their formation are still under investigation. Our previous studies revealed altered microRNA (miRNA) expression and DNA methylation levels in sarcoid tumors. Abnormal patterns of methylation may be responsible for changes in gene expression levels, including microRNAs. Recently, the DNA methylation of gene bodies has also been shown to have an impact on gene expression. Thus, the aim of the study was to investigate the methylation pattern of gene bodies of chosen miRNAs identified in sarcoid tissue (miR-101, miR-10b, miR-200a, and miR-338-3p), which have also been established to play roles in neoplastic transformation. To this end, we applied qRT-PCR, Bisulfite Sequencing PCR (BSP), and Mquant methods. As a result, we identified the statistically significant downregulation of pri-mir-101-1, pri-mir-10b, and pri-mir-200a in the sarcoid samples in comparison to the control. The DNA methylation analysis revealed their hypermethylation. This suggests that DNA methylation may be one mechanism responsible for the downregulation of theses miRNAs. However, the identified differences in the methylation levels are not very high, which implies that other mechanisms may also underlie the downregulation of the expression of these miRNAs in equine sarcoids. For the first time, the results obtained shed light on microRNA expression regulation by gene body methylation in equine sarcoids and provide bases for further deeper studies on other mechanisms influencing the miRNA repertoire. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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12 pages, 1361 KiB

Open AccessArticle

A Unique Spectrum of Spontaneous Tumors in Dino Knockout Mice Identifies Tissue-Specific Requirements for Tumor Suppression

by Christina B. Marney, Erik S. Anderson, Rachel Baum and Adam M. Schmitt

Cells 2022, 11(11), 1818; https://doi.org/10.3390/cells11111818 - 02 Jun 2022

Cited by 5 | Viewed by 1866

Abstract

Here, we report that Dino, a lncRNA required for p53 signaling, suppresses spontaneous tumorigenesis in mice. Dino^−/− mice develop significantly more malignant tumors than Dino^+/+ littermate controls, consisting predominantly of sarcomas, B cell lymphomas and additional rare tumors. While the prevalence [...] Read more.

Here, we report that Dino, a lncRNA required for p53 signaling, suppresses spontaneous tumorigenesis in mice. Dino^−/− mice develop significantly more malignant tumors than Dino^+/+ littermate controls, consisting predominantly of sarcomas, B cell lymphomas and additional rare tumors. While the prevalence of lymphomas and sarcomas in Dino^−/− mice is similar to that of mice with p53 loss, important distinctions emerged. p53-null mice predominantly develop T cell lymphomas; however, no spontaneous T cell lymphoma was observed in Dino^−/− mice. Rather than being a phenocopy of the p53-null tumor spectrum, spontaneous tumors in Dino^−/− mice resemble the spectrum of human cancers in which DINO is recurrently silenced by methylation in a manner that is mutually exclusive with TP53 alterations, suggesting that similar tissues in human and mouse require DINO for tumor suppression. Consistent with a tissue-specific role for Dino in tumor suppression, loss of Dino had no impact on the development of radiation-induced T cell lymphoma and oncogene-driven medulloblastoma, tumors that are accelerated by the loss of p53. Taken together, these data indicate that Dino serves as a potent tumor suppressor molecule specific to a select subset of tissues in mice and humans. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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20 pages, 5083 KiB

Open AccessArticle

LINC00152 Drives a Competing Endogenous RNA Network in Human Hepatocellular Carcinoma

by Rossella Pellegrino, Mirco Castoldi, Fabio Ticconi, Britta Skawran, Jan Budczies, Fabian Rose, Constantin Schwab, Kai Breuhahn, Ulf P. Neumann, Nadine T. Gaisa, Sven H. Loosen, Tom Luedde, Ivan G. Costa and Thomas Longerich

Cells 2022, 11(9), 1528; https://doi.org/10.3390/cells11091528 - 03 May 2022

Cited by 6 | Viewed by 2453

Abstract

Genomic and epigenomic studies revealed dysregulation of long non-coding RNAs in many cancer entities, including liver cancer. We identified an epigenetic mechanism leading to upregulation of the long intergenic non-coding RNA 152 (LINC00152) expression in human hepatocellular carcinoma (HCC). Here, we [...] Read more.

Genomic and epigenomic studies revealed dysregulation of long non-coding RNAs in many cancer entities, including liver cancer. We identified an epigenetic mechanism leading to upregulation of the long intergenic non-coding RNA 152 (LINC00152) expression in human hepatocellular carcinoma (HCC). Here, we aimed to characterize a potential competing endogenous RNA (ceRNA) network, in which LINC00152 exerts oncogenic functions by sponging miRNAs, thereby affecting their target gene expression. Database and gene expression data of human HCC were integrated to develop a potential LINC00152-driven ceRNA in silico. RNA immunoprecipitation and luciferase assay were used to identify miRNA binding to LINC00152 in human HCC cells. Functionally active players in the ceRNA network were analyzed using gene editing, siRNA or miRNA mimic transfection, and expression vectors in vitro. RNA expression in human HCC in vivo was validated by RNA in situ hybridization. Let-7c-5p, miR-23a-3p, miR-125a-5p, miR-125b-5p, miR-143a-3p, miR-193-3p, and miR-195-5p were detected as new components of the potential LINC00152 ceRNA network in human HCC. LINC00152 was confirmed to sponge miR143a-3p in human HCC cell lines, thereby limiting its binding to their respective target genes, like KLC2. KLC2 was identified as a central mediator promoting pro-tumorigenic effects of LINC00152 overexpression in HCC cells. Furthermore, co-expression of LINC00152 and KLC2 was observed in human HCC cohorts and high KLC2 expression was associated with shorter patient survival. Functional assays demonstrated that KLC2 promoted cell proliferation, clonogenicity and migration in vitro. The LINC00152-miR-143a-3p-KLC2 axis may represent a therapeutic target in human HCC. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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18 pages, 3283 KiB

Open AccessArticle

The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers

by Richard Molnar, Laszlo Szabo, Andras Tomesz, Arpad Deutsch, Richard Darago, Bence L. Raposa, Nowrasteh Ghodratollah, Timea Varjas, Balazs Nemeth, Zsuzsanna Orsos, Eva Pozsgai, Jozsef L. Szentpeteri, Ferenc Budan and Istvan Kiss

Cells 2022, 11(8), 1300; https://doi.org/10.3390/cells11081300 - 12 Apr 2022

Cited by 8 | Viewed by 2462

Abstract

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry ( [...] Read more.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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18 pages, 3821 KiB

Open AccessArticle

Long Noncoding RNA LOC550643 Acts as an Oncogene in the Growth Regulation of Colorectal Cancer Cells

by Hsuan Franziska Wu, Tzung-Ju Lu, Yi-Hao Lo, Ya-Ting Tu, Yi-Ru Chen, Ming-Cheng Lee, Yu-Lun Chiang, Chung-Yu Yeh and Kuo-Wang Tsai

Cells 2022, 11(7), 1065; https://doi.org/10.3390/cells11071065 - 22 Mar 2022

Cited by 4 | Viewed by 1722

Abstract

Long noncoding RNAs play a key role in the progression of colorectal cancer (CRC). However, the role and mechanism of LOC550643 in CRC cell growth and metastasis remain largely unknown. In this study, we assessed the clinical impacts of LOC550643 on CRC through [...] Read more.

Long noncoding RNAs play a key role in the progression of colorectal cancer (CRC). However, the role and mechanism of LOC550643 in CRC cell growth and metastasis remain largely unknown. In this study, we assessed the clinical impacts of LOC550643 on CRC through the analysis of The Cancer Genome Atlas database, which revealed the significant upregulation of LOC550643 in CRC. Moreover, the high expression of LOC550643 was associated with poor survival in patients with CRC (p = 0.001). Multivariate Cox regression analysis indicated that LOC550643 overexpression was an independent prognostic factor for shorter overall survival in patients with CRC (adjusted hazard ratio, 1.90; 95% confidence interval, 1.21–3.00; p = 0.006). A biological function analysis revealed that LOC550643 knockdown reduced colon cancer cell growth by hindering cell cycle progression. In addition, LOC550643 knockdown significantly induced cell apoptosis through the inhibition of signaling activity in phosphoinositide 3-kinases. Moreover, LOC550643 knockdown contributed to the inhibition of migration and invasion ability in colon cancer cells. Furthermore, miR-29b-2-5p interacted with the LOC550643 sequence. Ectopic miR-29b-2-5p significantly suppressed colon cancer cell growth and motility and induced cell apoptosis. Our findings suggest that, LOC550643–miR-29b-2-5p axis was determined to participate in the growth and metastasis of colon cancer cells; this could serve as a useful molecular biomarker for cancer diagnosis and as a potential therapeutic target for CRC. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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13 pages, 2557 KiB

Open AccessArticle

Changes in miR-124-1, miR-212, miR-132, miR-134, and miR-155 Expression Patterns after 7,12-Dimethylbenz(a)anthracene Treatment in CBA/Ca Mice

by Andras Tomesz, Laszlo Szabo, Richard Molnar, Arpad Deutsch, Richard Darago, Bence L. Raposa, Nowrasteh Ghodratollah, Timea Varjas, Balazs Nemeth, Zsuzsanna Orsos, Eva Pozsgai, Jozsef L. Szentpeteri, Ferenc Budan and Istvan Kiss

Cells 2022, 11(6), 1020; https://doi.org/10.3390/cells11061020 - 17 Mar 2022

Cited by 4 | Viewed by 2247

Abstract

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, [...] Read more.

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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17 pages, 1991 KiB

Open AccessArticle

miRNA-Dependent Regulation of AKT1 Phosphorylation

by Mallory I. Frederick, Tarana Siddika, Pengcheng Zhang, Nileeka Balasuriya, Matthew A. Turk, Patrick O’Donoghue and Ilka U. Heinemann

Cells 2022, 11(5), 821; https://doi.org/10.3390/cells11050821 - 26 Feb 2022

Cited by 13 | Viewed by 3552

Abstract

The phosphoinositide-3-kinase (PI3K)/AKT pathway regulates cell survival and is over-activated in most human cancers, including ovarian cancer. Following growth factor stimulation, AKT1 is activated by phosphorylation at T308 and S473. Disruption of the AKT1 signaling pathway is sufficient to inhibit the epithelial-mesenchymal transition [...] Read more.

The phosphoinositide-3-kinase (PI3K)/AKT pathway regulates cell survival and is over-activated in most human cancers, including ovarian cancer. Following growth factor stimulation, AKT1 is activated by phosphorylation at T308 and S473. Disruption of the AKT1 signaling pathway is sufficient to inhibit the epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) cells. In metastatic disease, adherent EOC cells transition to a dormant spheroid state, characterized previously by low S473 phosphorylation in AKT1. We confirmed this finding and observed that T308 phosphorylation was yet further reduced in EOC spheroids and that the transition from adherent to spheroid growth is accompanied by significantly increased levels of let-7 miRNAs. We then used mechanistic studies to investigate the impact of let-7 miRNAs on AKT1 phosphorylation status and activity in cells. In growth factor-stimulated HEK 293T cells supplemented with let-7a, we found increased phosphorylation of AKT1 at T308, decreased phosphorylation at S473, and enhanced downstream AKT1 substrate GSK-3β phosphorylation. Let-7b and let-7g also deregulated AKT signaling by rendering AKT1 insensitive to growth factor simulation. We uncovered let-7a-dependent deregulation of PI3K pathway components, including PI3KC2A, PDK1, and RICTOR, that govern AKT1 phosphorylation and activity. Together, our data show a new role for miRNAs in regulating AKT signaling. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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Review

Jump to: Editorial, Research, Other

15 pages, 1343 KiB

Open AccessReview

The Two Faces of Immune-Related lncRNAs in Head and Neck Squamous Cell Carcinoma

by Lesly J. Bueno-Urquiza, Marcela G. Martínez-Barajas, Carlos E. Villegas-Mercado, Jonathan R. García-Bernal, Ana L. Pereira-Suárez, Maribel Aguilar-Medina and Mercedes Bermúdez

Cells 2023, 12(5), 727; https://doi.org/10.3390/cells12050727 - 24 Feb 2023

Cited by 5 | Viewed by 2218

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a group of cancers originating from the mucosal epithelium in the oral cavity, larynx, oropharynx, nasopharynx, and hypopharynx. Molecular factors can be key in the diagnosis, prognosis, and treatment of HNSCC patients. Long non-coding RNAs [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is a group of cancers originating from the mucosal epithelium in the oral cavity, larynx, oropharynx, nasopharynx, and hypopharynx. Molecular factors can be key in the diagnosis, prognosis, and treatment of HNSCC patients. Long non-coding RNAs (lncRNAs) are molecular regulators composed of 200 to 100,000 nucleotides that act on the modulation of genes that activate signaling pathways associated with oncogenic processes such as proliferation, migration, invasion, and metastasis in tumor cells. However, up until now, few studies have discussed the participation of lncRNAs in modeling the tumor microenvironment (TME) to generate a protumor or antitumor environment. Nevertheless, some immune-related lncRNAs have clinical relevance, since AL139158.2, AL031985.3, AC104794.2, AC099343.3, AL357519.1, SBDSP1, AS1AC108010.1, and TM4SF19-AS1 have been associated with overall survival (OS). MANCR is also related to poor OS and disease-specific survival. MiR31HG, TM4SF19-AS1, and LINC01123 are associated with poor prognosis. Meanwhile, LINC02195 and TRG-AS1 overexpression is associated with favorable prognosis. Moreover, ANRIL lncRNA induces resistance to cisplatin by inhibiting apoptosis. A superior understanding of the molecular mechanisms of lncRNAs that modify the characteristics of TME could contribute to increasing the efficacy of immunotherapy. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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24 pages, 3982 KiB

Open AccessReview

Circular RNAs—New Kids on the Block in Cancer Pathophysiology and Management

by Adrian Szczepaniak, Agnieszka Bronisz and Jakub Godlewski

Cells 2023, 12(4), 552; https://doi.org/10.3390/cells12040552 - 08 Feb 2023

Cited by 5 | Viewed by 1896

Abstract

The ever-increasing number of cancer cases and persistently high mortality underlines the urgent need to acquire new perspectives for developing innovative therapeutic approaches. As the research on protein-coding genes brought significant yet only incremental progress in the development of anticancer therapy, much attention [...] Read more.

The ever-increasing number of cancer cases and persistently high mortality underlines the urgent need to acquire new perspectives for developing innovative therapeutic approaches. As the research on protein-coding genes brought significant yet only incremental progress in the development of anticancer therapy, much attention is now devoted to understanding the role of non-coding RNAs (ncRNAs) in various types of cancer. Recent years have brought about the awareness that ncRNAs recognized previously as “dark matter” are, in fact, key players in shaping cancer development. Moreover, breakthrough discoveries concerning the role of a new group of ncRNAs, circular RNAs, have evidenced their high importance in many diseases, including malignancies. Therefore, in the following review, we focus on the role of circular RNAs in cancer, particularly in cancer stem-like cells, summarize their mechanisms of action, and provide an overview of the state-of-the-art toolkits to study them. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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18 pages, 1362 KiB

Open AccessReview

Potential miRNA Use as a Biomarker: From Breast Cancer Diagnosis to Metastasis

by Euclides Jordan-Alejandre, Alma D. Campos-Parra, Dora Luz Castro-López and Macrina Beatriz Silva-Cázares

Cells 2023, 12(4), 525; https://doi.org/10.3390/cells12040525 - 06 Feb 2023

Cited by 10 | Viewed by 3104

Abstract

Breast cancer is the most common cancer in women. Despite advances in diagnosis and prognosis, distal metastases occur in these patients in up to 15% of cases within 3 years of diagnosis. The main organs in which BC metastasises are the bones, lungs, [...] Read more.

Breast cancer is the most common cancer in women. Despite advances in diagnosis and prognosis, distal metastases occur in these patients in up to 15% of cases within 3 years of diagnosis. The main organs in which BC metastasises are the bones, lungs, liver, and brain. Unfortunately, 90% of metastatic patients will die, making this an incurable disease. Researchers are therefore seeking biomarkers for diagnosis and metastasis in different organs. Optimally, such biomarkers should be easy to detect using, preferably, non-invasive methods, such as using miRNA molecules, which are small molecules of about 22 nt that have as their main function the post-transcriptional regulation of genes. Furthermore, due to their uncomplicated detection and reproducibility in the laboratory, they are a tool of complementary interest for diagnosis, prognosis, and treatment. With this in mind, in this review, we focus on describing the most current studies that propose using miRNA independently as a potential biomarker for the diagnosis and prediction of brain, lung, liver, and bone metastases, as well as to open a window of opportunity to deepen this area of study to eventually use miRNAs molecules in clinical practice for the benefit of BC patients. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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12 pages, 1059 KiB

Open AccessReview

A Concise Review on Dysregulation of LINC00665 in Cancers

by Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Aria Baniahmad, Mohammad Taheri and Mohammadreza Hajiesmaeili

Cells 2022, 11(22), 3575; https://doi.org/10.3390/cells11223575 - 11 Nov 2022

Cited by 3 | Viewed by 1582

Abstract

Long Intergenic Non-Protein Coding RNA 665 (LINC00665) is an RNA gene located on the minus strand of chromosome 19. This lncRNA acts as a competing endogenous RNA for miR-4458, miR-379-5p, miR-551b-5p, miR-3619-5p, miR-424-5p, miR-9-5p, miR-214-3p, miR-126-5p, miR-149-3p, miR-379-5p, miR-665, miR-34a-5p, miR-186-5p, miR-138-5p, miR-181c-5p, [...] Read more.

Long Intergenic Non-Protein Coding RNA 665 (LINC00665) is an RNA gene located on the minus strand of chromosome 19. This lncRNA acts as a competing endogenous RNA for miR-4458, miR-379-5p, miR-551b-5p, miR-3619-5p, miR-424-5p, miR-9-5p, miR-214-3p, miR-126-5p, miR-149-3p, miR-379-5p, miR-665, miR-34a-5p, miR-186-5p, miR-138-5p, miR-181c-5p, miR-98, miR-195-5p, miR-224-5p, miR-3619, miR-708, miR-101, miR-1224-5p, miR-34a-5p, and miR-142-5p. Via influencing expression of these miRNAs, it can enhance expression of a number of oncogenes. Moreover, LINC00665 can influence activity of Wnt/β-Catenin, TGF-β, MAPK1, NF-κB, ERK, and PI3K/AKT signaling. Function of this lncRNA has been assessed through gain-of-function tests and/or loss-of-function studies. Furthermore, diverse research groups have evaluated its expression levels in tissue samples using microarray and RT-qPCR techniques. In this manuscript, we have summarized the results of these studies and categorized them in three sections, i.e., cell line studies, animal studies, and investigations in clinical samples. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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41 pages, 1598 KiB

Open AccessReview

Long Noncoding RNAs and Circular RNAs Regulate AKT and Its Effectors to Control Cell Functions of Cancer Cells

by Jen-Yang Tang, Ya-Ting Chuang, Jun-Ping Shiau, Kun-Han Yang, Fang-Rong Chang, Ming-Feng Hou, Ammad Ahmad Farooqi and Hsueh-Wei Chang

Cells 2022, 11(19), 2940; https://doi.org/10.3390/cells11192940 - 20 Sep 2022

Cited by 7 | Viewed by 3043

Abstract

AKT serine-threonine kinase (AKT) and its effectors are essential for maintaining cell proliferation, apoptosis, autophagy, endoplasmic reticulum (ER) stress, mitochondrial morphogenesis (fission/fusion), ferroptosis, necroptosis, DNA damage response (damage and repair), senescence, and migration of cancer cells. Several lncRNAs and circRNAs also regulate the [...] Read more.

AKT serine-threonine kinase (AKT) and its effectors are essential for maintaining cell proliferation, apoptosis, autophagy, endoplasmic reticulum (ER) stress, mitochondrial morphogenesis (fission/fusion), ferroptosis, necroptosis, DNA damage response (damage and repair), senescence, and migration of cancer cells. Several lncRNAs and circRNAs also regulate the expression of these functions by numerous pathways. However, the impact on cell functions by lncRNAs and circRNAs regulating AKT and its effectors is poorly understood. This review provides comprehensive information about the relationship of lncRNAs and circRNAs with AKT on the cell functions of cancer cells. the roles of several lncRNAs and circRNAs acting on AKT effectors, such as FOXO, mTORC1/2, S6K1/2, 4EBP1, SREBP, and HIF are explored. To further validate the relationship between AKT, AKT effectors, lncRNAs, and circRNAs, more predicted AKT- and AKT effector-targeting lncRNAs and circRNAs were retrieved from the LncTarD and circBase databases. Consistently, using an in-depth literature survey, these AKT- and AKT effector-targeting database lncRNAs and circRNAs were related to cell functions. Therefore, some lncRNAs and circRNAs can regulate several cell functions through modulating AKT and AKT effectors. This review provides insights into a comprehensive network of AKT and AKT effectors connecting to lncRNAs and circRNAs in the regulation of cancer cell functions. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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19 pages, 4257 KiB

Open AccessReview

From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer

by Jiho Rhim, Woosun Baek, Yoona Seo and Jong Heon Kim

Cells 2022, 11(18), 2791; https://doi.org/10.3390/cells11182791 - 07 Sep 2022

Cited by 22 | Viewed by 4509

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in regulating gene expression at a posttranscriptional level. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers, such as glioblastoma, pancreatic adenocarcinoma, [...] Read more.

MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in regulating gene expression at a posttranscriptional level. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers, such as glioblastoma, pancreatic adenocarcinoma, non-small cell lung cancer, and many others. MiR-21 targets many vital components in a wide range of cancers and acts on various cellular processes ranging from cancer stemness to cell death. Expression of miR-21 is elevated within cancer tissues and circulating miR-21 is readily detectable in biofluids, making it valuable as a cancer biomarker with significant potential for use in diagnosis and prognosis. Advances in RNA-based therapeutics have revealed additional avenues by which miR-21 can be utilized as a promising target in cancer. The purpose of this review is to outline the roles of miR-21 as a key modulator in various cancers and its potential as a therapeutic target. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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15 pages, 1138 KiB

Open AccessReview

Small Nucleolar RNAs and Their Comprehensive Biological Functions in Hepatocellular Carcinoma

by Xiaoyu Liu, Wan Xie, Silu Meng, Xiaoyan Kang, Yuhuan Liu, Lili Guo and Changyu Wang

Cells 2022, 11(17), 2654; https://doi.org/10.3390/cells11172654 - 26 Aug 2022

Cited by 2 | Viewed by 2854

Abstract

Small nucleolar RNAs (snoRNAs) are a class of highly conserved, stable non-coding RNAs involved in both post-transcriptional modification of RNA and in ribosome biogenesis. Recent research shows that the dysfunction of snoRNAs plays a pivotal role in hepatocellular carcinoma (HCC) and related etiologies, [...] Read more.

Small nucleolar RNAs (snoRNAs) are a class of highly conserved, stable non-coding RNAs involved in both post-transcriptional modification of RNA and in ribosome biogenesis. Recent research shows that the dysfunction of snoRNAs plays a pivotal role in hepatocellular carcinoma (HCC) and related etiologies, such as hepatitis B virus (HBV), hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD). Growing evidence suggests that snoRNAs act as oncogenes or tumor suppressors in hepatocellular carcinoma (HCC) through multiple mechanisms. Furthermore, snoRNAs are characterized by their stability in body fluids and their clinical relevance and represent promising tools as diagnostic and prognostic biomarkers. SnoRNAs represent an emerging area of cancer research. In this review, we summarize the classification, biogenesis, activity, and functions of snoRNAs, as well as highlight the mechanism and roles of snoRNAs in HCC and related diseases. Our findings will aid in the understanding of complex processes of tumor occurrence and development, as well as suggest potential diagnostic markers and treatment targets. Furthermore, we discuss several limitations and suggest future research and application directions. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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22 pages, 874 KiB

Open AccessReview

Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities

by Aditi Kulkarni, Sharan Gayathrinathan, Soumya Nair, Anamika Basu, Taslim A. Al-Hilal and Sourav Roy

Cells 2022, 11(15), 2448; https://doi.org/10.3390/cells11152448 - 07 Aug 2022

Cited by 2 | Viewed by 2492

Abstract

Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. [...] Read more.

Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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14 pages, 727 KiB

Open AccessReview

MicroRNAs as Indicators of Malignancy in Pancreatic Ductal Adenocarcinoma (PDAC) and Cystic Pancreatic Lesions

by Christian Prinz, Leonard Fehring and Robin Frese

Cells 2022, 11(15), 2374; https://doi.org/10.3390/cells11152374 - 02 Aug 2022

Cited by 8 | Viewed by 2369

Abstract

The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic lesions. In solid pancreatic tumor tissue, the dysregulation of miR-146, miR-196a/b, miR-198, miR-217, miR-409, and miR-490, as well as miR-1290 has been [...] Read more.

The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic lesions. In solid pancreatic tumor tissue, the dysregulation of miR-146, miR-196a/b, miR-198, miR-217, miR-409, and miR-490, as well as miR-1290 has been investigated in tumor biopsies of patients with PDAC and was reported to predict cancer presence. However, the value of the predictive biomarkers may further be increased during clinical conditions suggesting cancer development such as hyperinsulinemia or onset of diabetes. In this specific context, the dysregulation of miR-486 and miR-196 in tumors has been observed in the tumor tissue of PDAC patients with newly diagnosed diabetes mellitus. Moreover, miR-1256 is dysregulated in pancreatic cancer, possibly due to the interaction with long non-coding RNA molecules that seem to affect cell-cycle control and diabetes manifestation in PDAC patients, and, thus, these three markers may be of special or “sentinel value”. In blood samples, Next-generation sequencing (NGS) has also identified a set of microRNAs (miR-20a, miR-31-5p, miR-24, miR-25, miR-99a, miR-185, and miR-191) that seem to differentiate patients with pancreatic cancer remarkably from healthy controls, but limited data exist in this context regarding the prediction of cancer presences and outcomes. In contrast to solid pancreatic tumors, in cystic pancreatic cancer lesions, as well as premalignant lesions (such as intraductal papillary neoplasia (IPMN) or mucinous-cystic adenomatous cysts (MCAC)), the dysregulation of a completely different expression panel of miR-31-5p, miR-483-5p, miR-99a-5p, and miR-375 has been found to be of high clinical value in differentiating benign from malignant lesions. Interestingly, signal transduction pathways associated with miR-dysregulation seem to be entirely different in patients with pancreatic cysts when compared to PDAC. Overall, the determination of these different dysregulation “panels” in solid tumors, pancreatic cysts, obtained via fine-needle aspirate biopsies and/or in blood samples at the onset or during the treatment of pancreatic diseases, seems to be a reasonable candidate approach for predicting cancer presence, cancer development, and even therapy responses. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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19 pages, 1713 KiB

Open AccessReview

Regulation of the Cancer Stem Phenotype by Long Non-Coding RNAs

by Jose Adan Gutierrez-Cruz, Vilma Maldonado and Jorge Melendez-Zajgla

Cells 2022, 11(15), 2352; https://doi.org/10.3390/cells11152352 - 30 Jul 2022

Cited by 4 | Viewed by 2696

Abstract

Cancer stem cells are a cell population within malignant tumors that are characterized by the ability to self-renew, the presence of specific molecules that define their identity, the ability to form malignant tumors in vivo, resistance to drugs, and the ability to invade [...] Read more.

Cancer stem cells are a cell population within malignant tumors that are characterized by the ability to self-renew, the presence of specific molecules that define their identity, the ability to form malignant tumors in vivo, resistance to drugs, and the ability to invade and migrate to other regions of the body. These characteristics are regulated by various molecules, such as lncRNAs, which are transcripts that generally do not code for proteins but regulate multiple biological processes through various mechanisms of action. LncRNAs, such as HOTAIR, H19, LncTCF7, LUCAT1, MALAT1, LINC00511, and FMR1-AS1, have been described as key regulators of stemness in cancer, allowing cancer cells to acquire this phenotype. It has been proposed that cancer stem cells are clinically responsible for the high recurrence rates after treatment and the high frequency of metastasis in malignant tumors, so understanding the mechanisms that regulate the stem phenotype could have an impact on the improvement of cancer treatments. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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24 pages, 5665 KiB

Open AccessReview

Examples of Inverse Comorbidity between Cancer and Neurodegenerative Diseases: A Possible Role for Noncoding RNA

by Michele Salemi, Maria Paola Mogavero, Giuseppe Lanza, Laura M. Mongioì, Aldo E. Calogero and Raffaele Ferri

Cells 2022, 11(12), 1930; https://doi.org/10.3390/cells11121930 - 15 Jun 2022

Cited by 17 | Viewed by 3513

Abstract

Cancer is one of the most common causes of death; in parallel, the incidence and prevalence of central nervous system diseases are equally high. Among neurodegenerative diseases, Alzheimer’s dementia is the most common, while Parkinson’s disease (PD) is the second most frequent neurodegenerative [...] Read more.

Cancer is one of the most common causes of death; in parallel, the incidence and prevalence of central nervous system diseases are equally high. Among neurodegenerative diseases, Alzheimer’s dementia is the most common, while Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. There is a significant amount of evidence on the complex biological connection between cancer and neurodegeneration. Noncoding RNAs (ncRNAs) are defined as transcribed nucleotides that perform a variety of regulatory functions. The mechanisms by which ncRNAs exert their functions are numerous and involve every aspect of cellular life. The same ncRNA can act in multiple ways, leading to different outcomes; in fact, a single ncRNA can participate in the pathogenesis of more than one disease—even if these seem very different, as cancer and neurodegenerative disorders are. The ncRNA activates specific pathways leading to one or the other clinical phenotype, sometimes with obvious mechanisms of inverse comorbidity. We aimed to collect from the existing literature examples of inverse comorbidity in which ncRNAs seem to play a key role. We also investigated the example of mir-519a-3p, and one of its target genes Poly (ADP-ribose) polymerase 1, for the inverse comorbidity mechanism between some cancers and PD. We believe it is very important to study the inverse comorbidity relationship between cancer and neurodegenerative diseases because it will help us to better assess these two major areas of human disease. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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19 pages, 3206 KiB

Open AccessReview

HypoxaMIRs: Key Regulators of Hallmarks of Colorectal Cancer

by Jossimar Coronel-Hernández, Izamary Delgado-Waldo, David Cantú de León, César López-Camarillo, Nadia Jacobo-Herrera, Rosalío Ramos-Payán and Carlos Pérez-Plasencia

Cells 2022, 11(12), 1895; https://doi.org/10.3390/cells11121895 - 11 Jun 2022

Cited by 5 | Viewed by 2681

Abstract

Hypoxia in cancer is a thoroughly studied phenomenon, and the logical cause of the reduction in oxygen tension is tumor growth itself. While sustained hypoxia leads to death by necrosis in cells, there is an exquisitely regulated mechanism that rescues hypoxic cells from [...] Read more.

Hypoxia in cancer is a thoroughly studied phenomenon, and the logical cause of the reduction in oxygen tension is tumor growth itself. While sustained hypoxia leads to death by necrosis in cells, there is an exquisitely regulated mechanism that rescues hypoxic cells from their fatal fate. The accumulation in the cytoplasm of the transcription factor HIF-1α, which, under normoxic conditions, is marked for degradation by a group of oxygen-sensing proteins known as prolyl hydroxylases (PHDs) in association with the von Hippel-Lindau anti-oncogene (VHL) is critical for the cell, as it regulates different mechanisms through the genes it induces. A group of microRNAs whose expression is regulated by HIF, collectively called hypoxaMIRs, have been recognized. In this review, we deal with the hypoxaMIRs that have been shown to be expressed in colorectal cancer. Subsequently, using data mining, we analyze a panel of hypoxaMIRs expressed in both normal and tumor tissues obtained from TCGA. Finally, we assess the impact of these hypoxaMIRs on cancer hallmarks through their target genes. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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14 pages, 1289 KiB

Open AccessReview

Transcribed Ultraconserved Regions in Cancer

by Myron K. Gibert, Jr., Aditya Sarkar, Bilhan Chagari, Christian Roig-Laboy, Shekhar Saha, Sylwia Bednarek, Benjamin Kefas, Farina Hanif, Kadie Hudson, Collin Dube, Ying Zhang and Roger Abounader

Cells 2022, 11(10), 1684; https://doi.org/10.3390/cells11101684 - 19 May 2022

Cited by 3 | Viewed by 2276

Abstract

Transcribed ultraconserved regions are putative lncRNA molecules that are transcribed from DNA that is 100% conserved in human, mouse, and rat genomes. This is notable, as lncRNAs are typically poorly conserved. TUCRs remain very understudied in many diseases, including cancer. In this review, [...] Read more.

Transcribed ultraconserved regions are putative lncRNA molecules that are transcribed from DNA that is 100% conserved in human, mouse, and rat genomes. This is notable, as lncRNAs are typically poorly conserved. TUCRs remain very understudied in many diseases, including cancer. In this review, we summarize the current literature on TUCRs in cancer with respect to expression deregulation, functional roles, mechanisms of action, and clinical perspectives. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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14 pages, 611 KiB

Open AccessReview

The Role of Hypoxia-Associated Long Non-Coding RNAs in Breast Cancer

by Vilma Maldonado and Jorge Melendez-Zajgla

Cells 2022, 11(10), 1679; https://doi.org/10.3390/cells11101679 - 18 May 2022

Cited by 6 | Viewed by 2049

Abstract

Breast cancer is the leading cause of cancer-related deaths in women worldwide. In the United States, even with earlier diagnosis and treatment improvements, the decline in mortality has stagnated in recent years. More research is needed to provide better diagnostic, prognostic, and therapeutic [...] Read more.

Breast cancer is the leading cause of cancer-related deaths in women worldwide. In the United States, even with earlier diagnosis and treatment improvements, the decline in mortality has stagnated in recent years. More research is needed to provide better diagnostic, prognostic, and therapeutic tools for these patients. Long non-coding RNAs are newly described molecules that have extensive roles in breast cancer. Emerging reports have shown that there is a strong link between these RNAs and the hypoxic response of breast cancer cells, which may be an important factor for enhanced tumoral progression. In this review, we summarize the role of hypoxia-associated lncRNAs in the classic cancer hallmarks, describing their effects on the upstream and downstream hypoxia signaling pathway and the use of them as diagnostic and prognostic tools. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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18 pages, 1126 KiB

Open AccessReview

The Role of MiR-181 Family Members in Endothelial Cell Dysfunction and Tumor Angiogenesis

by Chun Yang, Victor Passos Gibson and Pierre Hardy

Cells 2022, 11(10), 1670; https://doi.org/10.3390/cells11101670 - 18 May 2022

Cited by 8 | Viewed by 2586

Abstract

Endothelial dysfunction plays a critical role in many human angiogenesis-related diseases, including cancer and retinopathies. Small non-coding microRNAs (miRNAs) repress gene expression at the post-transcriptional level. They are critical for endothelial cell gene expression and function and are involved in many pathophysiological processes. [...] Read more.

Endothelial dysfunction plays a critical role in many human angiogenesis-related diseases, including cancer and retinopathies. Small non-coding microRNAs (miRNAs) repress gene expression at the post-transcriptional level. They are critical for endothelial cell gene expression and function and are involved in many pathophysiological processes. The miR-181 family is one of the essential angiogenic regulators. This review summarizes the current state of knowledge of the role of miR-181 family members in endothelial cell dysfunction, with emphasis on their pathophysiological roles in aberrant angiogenesis. The actions of miR-181 members are summarized concerning their targets and associated major angiogenic signaling pathways in a cancer-specific context. Elucidating the underlying functional mechanisms of miR-181 family members that are dysregulated in endothelial cells or cancer cells is invaluable for developing miRNA-based therapeutics for angiogenesis-related diseases such as retinopathies, angiogenic tumors, and cancer. Finally, potential clinical applications of miR-181 family members in anti-angiogenic tumor therapy are discussed. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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24 pages, 770 KiB

Open AccessReview

Long Non-Coding RNAs as Novel Biomarkers in the Clinical Management of Papillary Renal Cell Carcinoma Patients: A Promise or a Pledge?

by Francesco Trevisani, Matteo Floris, Riccardo Vago, Roberto Minnei and Alessandra Cinque

Cells 2022, 11(10), 1658; https://doi.org/10.3390/cells11101658 - 17 May 2022

Cited by 5 | Viewed by 2908

Abstract

Papillary renal cell carcinoma (pRCC) represents the second most common subtype of renal cell carcinoma, following clear cell carcinoma and accounting for 10–15% of cases. For around 20 years, pRCCs have been classified according to their mere histopathologic appearance, unsupported by genetic and [...] Read more.

Papillary renal cell carcinoma (pRCC) represents the second most common subtype of renal cell carcinoma, following clear cell carcinoma and accounting for 10–15% of cases. For around 20 years, pRCCs have been classified according to their mere histopathologic appearance, unsupported by genetic and molecular evidence, with an unmet need for clinically relevant classification. Moreover, patients with non-clear cell renal cell carcinomas have been seldom included in large clinical trials; therefore, the therapeutic landscape is less defined than in the clear cell subtype. However, in the last decades, the evolving comprehension of pRCC molecular features has led to a growing use of target therapy and to better oncological outcomes. Nonetheless, a reliable molecular biomarker able to detect the aggressiveness of pRCC is not yet available in clinical practice. As a result, the pRCC correct prognosis remains cumbersome, and new biomarkers able to stratify patients upon risk of recurrence are strongly needed. Non-coding RNAs (ncRNAs) are functional elements which play critical roles in gene expression, at the epigenetic, transcriptional, and post-transcriptional levels. In the last decade, ncRNAs have gained importance as possible biomarkers for several types of diseases, especially in the cancer universe. In this review, we analyzed the role of long non-coding RNAs (lncRNAs) in the prognosis of pRCC, with a particular focus on their networking. In fact, in the competing endogenous RNA hypothesis, lncRNAs can bind miRNAs, resulting in the modulation of the mRNA levels targeted by the sponged miRNA, leading to additional regulation of the target gene expression and increasing complexity in the biological processes. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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20 pages, 1381 KiB

Open AccessReview

The Regulatory Functions and the Mechanisms of Long Non-Coding RNAs in Cervical Cancer

by Qiwei Yang and Ayman Al-Hendy

Cells 2022, 11(7), 1149; https://doi.org/10.3390/cells11071149 - 29 Mar 2022

Cited by 20 | Viewed by 3540

Abstract

Cervical cancer is one of the leading causes of death in gynecology cancer worldwide. High-risk human papillomaviruses (HPVs) are the major etiological agents for cervical cancer. Still, other factors also contribute to cervical cancer development because these cancers commonly arise decades after initial [...] Read more.

Cervical cancer is one of the leading causes of death in gynecology cancer worldwide. High-risk human papillomaviruses (HPVs) are the major etiological agents for cervical cancer. Still, other factors also contribute to cervical cancer development because these cancers commonly arise decades after initial exposure to HPV. So far, the molecular mechanisms underlying the pathogenesis of cervical cancer are still quite limited, and a knowledge gap needs to be filled to help develop novel strategies that will ultimately facilitate the development of therapies and improve cervical cancer patient outcomes. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation, and the relevant role of lncRNAs in cervical cancer has recently been investigated. In this review, we summarize the recent progress in ascertaining the biological functions of lncRNAs in cervical cancer from the perspective of cervical cancer proliferation, invasion, and metastasis. In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of lncRNAs in the pathogenesis of cervical cancer. Comprehensive and deeper insights into lncRNA-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with cervical cancer. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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24 pages, 3116 KiB

Open AccessReview

MicroRNA as a Potential Therapeutic Molecule in Cancer

by Joanna Szczepanek, Monika Skorupa and Andrzej Tretyn

Cells 2022, 11(6), 1008; https://doi.org/10.3390/cells11061008 - 16 Mar 2022

Cited by 42 | Viewed by 3917

Abstract

Small noncoding RNAs, as post-translational regulators of many target genes, are not only markers of neoplastic disease initiation and progression, but also markers of response to anticancer therapy. Hundreds of miRNAs have been identified as biomarkers of drug resistance, and many have demonstrated [...] Read more.

Small noncoding RNAs, as post-translational regulators of many target genes, are not only markers of neoplastic disease initiation and progression, but also markers of response to anticancer therapy. Hundreds of miRNAs have been identified as biomarkers of drug resistance, and many have demonstrated the potential to sensitize cancer cells to therapy. Their properties of modulating the response of cells to therapy have made them a promising target for overcoming drug resistance. Several methods have been developed for the delivery of miRNAs to cancer cells, including introducing synthetic miRNA mimics, DNA plasmids containing miRNAs, and small molecules that epigenetically alter endogenous miRNA expression. The results of studies in animal models and preclinical studies for solid cancers and hematological malignancies have confirmed the effectiveness of treatment protocols using microRNA. Nevertheless, the use of miRNAs in anticancer therapy is not without limitations, including the development of a stable nanoconstruct, delivery method choices, and biodistribution. The aim of this review was to summarize the role of miRNAs in cancer treatment and to present new therapeutic concepts for these molecules. Supporting anticancer therapy with microRNA molecules has been verified in numerous clinical trials, which shows great potential in the treatment of cancer. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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20 pages, 1654 KiB

Open AccessReview

Noncoding RNAs of Extracellular Vesicles in Tumor Angiogenesis: From Biological Functions to Clinical Significance

by Miao Hu, Juan Li, Chen-Guang Liu, Robby Miguel W. J. Goh, Fenggang Yu, Zhaowu Ma and Lingzhi Wang

Cells 2022, 11(6), 947; https://doi.org/10.3390/cells11060947 - 10 Mar 2022

Cited by 7 | Viewed by 2586

Abstract

Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis, which is a highly regulated multi-step process for the formation of new blood vessels that contribute to tumor proliferation. EVs induce malignant transformation [...] Read more.

Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis, which is a highly regulated multi-step process for the formation of new blood vessels that contribute to tumor proliferation. EVs induce malignant transformation of distinct cells by transferring DNAs, proteins, lipids, and RNAs, including noncoding RNAs (ncRNAs). However, the functional relevance of EV-derived ncRNAs in tumor angiogenesis remains to be elucidated. In this review, we summarized current research progress on the biological functions and underlying mechanisms of EV-derived ncRNAs in tumor angiogenesis in various cancers. In addition, we comprehensively discussed the potential applications of EV-derived ncRNAs as cancer biomarkers and novel therapeutic targets to tailor anti-angiogenic therapy. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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14 pages, 1550 KiB

Open AccessReview

MicroRNA-139, an Emerging Gate-Keeper in Various Types of Cancer

by Christiaan J. Stavast, Iris van Zuijen and Stefan J. Erkeland

Cells 2022, 11(5), 769; https://doi.org/10.3390/cells11050769 - 22 Feb 2022

Cited by 3 | Viewed by 2277

Abstract

Mounting data show that MIR139 is commonly silenced in solid cancer and hematological malignancies. MIR139 acts as a critical tumor suppressor by tuning the cellular response to different types of stress, including DNA damage, and by repressing oncogenic signaling pathways. Recently, novel insights [...] Read more.

Mounting data show that MIR139 is commonly silenced in solid cancer and hematological malignancies. MIR139 acts as a critical tumor suppressor by tuning the cellular response to different types of stress, including DNA damage, and by repressing oncogenic signaling pathways. Recently, novel insights into the mechanism of MIR139 silencing in tumor cells have been described. These include epigenetic silencing, inhibition of POL-II transcriptional activity on gene regulatory elements, enhanced expression of competing RNAs and post-transcriptional regulation by the microprocessor complex. Some of these MIR139-silencing mechanisms have been demonstrated in different types of cancer, suggesting that these are more general oncogenic events. Reactivation of MIR139 expression in tumor cells causes inhibition of tumor cell expansion and induction of cell death by the repression of oncogenic mRNA targets. In this review, we discuss the different aspects of MIR139 as a tumor suppressor gene and give an overview on different transcriptional mechanisms regulating MIR139 in oncogenic stress and across different types of cancer. The novel insights into the expression regulation and the tumor-suppressing activities of MIR139 may pave the way to new treatment options for cancer. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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19 pages, 2179 KiB

Open AccessReview

Three-Dimensional Genome Organization in Breast and Gynecological Cancers: How Chromatin Folding Influences Tumorigenic Transcriptional Programs

by Stephanie I. Nuñez-Olvera, Jonathan Puente-Rivera, Rosalio Ramos-Payán, Carlos Pérez-Plasencia, Yarely M. Salinas-Vera, Lorena Aguilar-Arnal and César López-Camarillo

Cells 2022, 11(1), 75; https://doi.org/10.3390/cells11010075 - 28 Dec 2021

Cited by 4 | Viewed by 3939

Abstract

A growing body of research on the transcriptome and cancer genome has demonstrated that many gynecological tumor-specific gene mutations are located in cis-regulatory elements. Through chromosomal looping, cis-regulatory elements interact which each other to control gene expression by bringing distant regulatory elements, such [...] Read more.

A growing body of research on the transcriptome and cancer genome has demonstrated that many gynecological tumor-specific gene mutations are located in cis-regulatory elements. Through chromosomal looping, cis-regulatory elements interact which each other to control gene expression by bringing distant regulatory elements, such as enhancers and insulators, into close proximity with promoters. It is well known that chromatin connections may be disrupted in cancer cells, promoting transcriptional dysregulation and the expression of abnormal tumor suppressor genes and oncogenes. In this review, we examine the roles of alterations in 3D chromatin interactions. This includes changes in CTCF protein function, cancer-risk single nucleotide polymorphisms, viral integration, and hormonal response as part of the mechanisms that lead to the acquisition of enhancers or super-enhancers. The translocation of existing enhancers, as well as enhancer loss or acquisition of insulator elements that interact with gene promoters, is also revised. Remarkably, similar processes that modify 3D chromatin contacts in gene promoters may also influence the expression of non-coding RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), which have emerged as key regulators of gene expression in a variety of cancers, including gynecological malignancies. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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25 pages, 1253 KiB

Open AccessSystematic Review

Clinical Value and Molecular Function of Circulating MicroRNAs in Endometrial Cancer Regulation: A Systematic Review

by Joy Bloomfield, Michèle Sabbah, Mathieu Castela, Céline Mehats, Catherine Uzan and Geoffroy Canlorbe

Cells 2022, 11(11), 1836; https://doi.org/10.3390/cells11111836 - 03 Jun 2022

Cited by 7 | Viewed by 2284

Abstract

This systematic review of literature highlights the different microRNAs circulating in the serum or plasma of endometrial cancer patients and their association with clinical and prognostic characteristics in endometrial cancer. This study also investigates the molecular functions of these circulating microRNAs. According to [...] Read more.

This systematic review of literature highlights the different microRNAs circulating in the serum or plasma of endometrial cancer patients and their association with clinical and prognostic characteristics in endometrial cancer. This study also investigates the molecular functions of these circulating microRNAs. According to this systematic review, a total of 33 individual circulating miRs (-9, -15b, -20b-5p, -21, -27a, -29b, -30a-5p, -92a, -99a, -100, -135b, -141, -142-3p, -143-3p, -146a-5p, -150-5p, -151a-5p, -186, -195-5p, -199b, -200a, -203, -204, -205, -222, -223, -301b, -423-3p, -449, -484, -887-5p, -1228, and -1290) and 6 different panels of miRs (“miR-222/miR-223/miR-186/miR-204”, “miR-142-3p/miR-146a-5p/miR-151a-5p”, “miR-143-3p/miR-195-5p/miR-20b-5p/miR-204-5p/miR-423-3p/miR-484”, “mir-9/miR-1229”, “miR-9/miR-92a”, and “miR-99a/miR-199b”) had a significant expression variation in EC patients compared to healthy patients. Also, seven individual circulating miRs (-9, -21, -27a, -29b, -99a, -142-3p, and -449a) had a significant expression variation according to EC prognostic factors such as the histological type and grade, tumor size, FIGO stage, lymph node involvement, and survival rates. One panel of circulating miRs (“-200b/-200c/-203/-449a”) had a significant expression variation according to EC myometrial invasion. Further studies are needed to better understand their function and circulation. Full article

(This article belongs to the Special Issue Regulatory Roles of Non-coding RNAs in Cancer)

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