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The Role of MicroRNA in Cancer

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (20 October 2021) | Viewed by 40892

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Special Issue Editors

Prof. Dr. Edoardo Alesse

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Guest Editor

Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
Interests: general and molecular pathology; cancer molecular pathogenesis; microRNA; cell cycle; apoptosis; inflammation
Special Issues, Collections and Topics in MDPI journals

Dr. Francesca Zazzeroni

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Co-Guest Editor

Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
Interests: cancer molecular pathogenesis; inflammation; NF-kB signaling; apoptosis; preclinical models; new therapeutic targets identification; epatocarcinogenesis; neurodegenerative eye and ear diseases; microRNA
Special Issues, Collections and Topics in MDPI journals

Dr. Alessandra Tessitore

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Co-Guest Editor

Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
Interests: cancer molecular pathogenesis and diagnostics; personalized medicine; epatocarcinogenesis; neurodegenerative eye and ear diseases; microRNA; profiling analysis; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

During the last decade, three classes of non-coding RNAs gained great attention. Among them, microRNAs, short (18-22 nucleotide in length) endogenous non-coding RNAs, play a role in regulating the expression of target genes at the post-transcriptional level. MicroRNAs are involved in the control of fundamental cell processes, such as growth, proliferation, differentiation, cell cycle, and programmed death. Dysregulation or aberrant microRNAs’ expression levels and different profiles are described in important pathological conditions, such as cardiovascular, neurological diseases, and cancer. It is known that tumour initiation, progression, and metastasis dissemination are correlated to significant changes in gene expression; for this reason, in the last decade, a large and increasing number of studies has been focused on examining in depth the role of microRNAs in tumorigenesis. Depending on the function of target genes, microRNAs can show tumour promoting (oncomiR) or suppressive (tumor suppressor miRs) properties in cancers, by regulating the expression of entire groups of genes implicated in oncogenesis and metastasis. MicroRNAs are considered as early diagnostic, prognostic, and predictive biomarkers as well. In addition, dysregulated miRNAs produced in the tumour microenvironment can be released into the bloodstream because of passive or active mechanisms. Due to their structure and nature, circulating microRNAs are resistant to endogenous RNase and very stable even in difficult conditions; for this reason, they are considered as suitable and promising non-invasive biomarkers. Novel therapeutic anti-cancer strategies are directed to target dysregulated/aberrantly expressed key microRNAs to re-establish normal physiological conditions, by inhibiting or restoring their normal expression levels. To this aim, the identification of improved and effective delivery systems is of great relevance. Importantly, such new generation- targeted therapies might be considered in combination regimens or as secondary treatment in cancers which are unresponsive to conventional therapeutic schemes.

In this Special Issue, we are interested in recent advances and opinions on the role of non-coding RNAs in oncogenesis. Research papers and reviews will focus on, but are not limited to, the role of microRNAs in tumorigenesis; microRNAs as biomarkers in cancer; therapeutic use of microRNAs in cancer, strategies and delivery systems to restore microRNA expression levels; microRNA preclinical models and bioinformatics approaches for miRNAs/target genes analysis.

Prof. Edoardo Alesse
Guest Editor
Prof. Francesca Zazzeroni
Dr. Alessandra Tessitore
Co-Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

non-coding RNAs
cancer
biomarkers
preclinical models
targetome
microRNA-based therapy

Published Papers (14 papers)

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17 pages, 3316 KiB

Open AccessArticle

Identification of miR-199-5p and miR-199-3p Target Genes: Paxillin Facilities Cancer Cell Aggressiveness in Head and Neck Squamous Cell Carcinoma

by Nozomi Tanaka, Chikashi Minemura, Shunichi Asai, Naoko Kikkawa, Takashi Kinoshita, Sachi Oshima, Ayaka Koma, Atsushi Kasamatsu, Toyoyuki Hanazawa, Katsuhiro Uzawa and Naohiko Seki

Genes 2021, 12(12), 1910; https://doi.org/10.3390/genes12121910 - 27 Nov 2021

Cited by 10 | Viewed by 2136

Abstract

Our previous study revealed that the miR-199 family (miR-199a-5p/-3p and miR-199b-5p/-3p) acts as tumor-suppressive miRNAs in head and neck squamous cell carcinoma (HNSCC). Furthermore, recent studies have indicated that the passenger strands of miRNAs are involved in cancer pathogenesis. The aim of this study was to identify cancer-promoting genes commonly regulated by miR-199-5p and miR-199-3p in HNSCC cells. Our in silico analysis and luciferase reporter assay identified paxillin (PXN) as a direct target of both miR-199-5p and miR-199-3p in HNSCC cells. Analysis of the cancer genome atlas (TCGA) database showed that expression of PXN significantly predicted a worse prognosis (5-year overall survival rate; p = 0.0283). PXN expression was identified as an independent factor predicting patient survival according to multivariate Cox regression analyses (p = 0.0452). Overexpression of PXN was detected in HNSCC clinical specimens by immunostaining. Functional assays in HNSCC cells showed that knockdown of PXN expression attenuated cancer cell migration and invasion, suggesting that aberrant expression of PXN contributed to HNSCC cell aggressiveness. Our miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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16 pages, 1349 KiB

Open AccessArticle

Ultrasound-Based Method for the Identification of Novel MicroRNA Biomarkers in Prostate Cancer

by Jessica Cornice, Daria Capece, Mauro Di Vito Nolfi, Monica Di Padova, Chiara Compagnoni, Daniela Verzella, Barbara Di Francesco, Davide Vecchiotti, Irene Flati, Alessandra Tessitore, Edoardo Alesse, Gaetano Barbato and Francesca Zazzeroni

Genes 2021, 12(11), 1726; https://doi.org/10.3390/genes12111726 - 28 Oct 2021

Cited by 1 | Viewed by 2013

Abstract

The detection of circulating microRNA (miRNA)-based biomarkers represents an innovative, non-invasive method for the early detection of cancer. However, the low concentration of miRNAs released in body fluids and the difficult identification of the tumor site have limited their clinical use as effective cancer biomarkers. To evaluate if ultrasound treatment could amplify the release of extracellular cancer biomarkers, we treated a panel of prostate cancer (PCa) cell lines with an ultrasound-based prototype and profiled the release of miRNAs in the extracellular space, with the aim of identifying novel miRNA-based biomarkers that could be used for PCa diagnosis and the monitoring of tumor evolution. We provide evidence that US-mediated sonoporation amplifies the release of miRNAs from both androgen-dependent (AD) and -independent (AI) PCa cells. We identified four PCa-related miRNAs, whose levels in LNCaP and DU145 supernatants were significantly increased following ultrasound treatment: mir-629-5p, mir-374-5p, mir-194-5p, and let-7d-5p. We further analyzed a publicly available dataset of PCa, showing that the serum expression of these novel miRNAs was upregulated in PCa patients compared to controls, thus confirming their clinical relevance. Our findings highlight the potential of using ultrasound to identify novel cell-free miRNAs released from cancer cells, with the aim of developing new biomarkers with diagnostic and predictive value. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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18 pages, 9413 KiB

Open AccessArticle

NOV/CCN3 Promotes Cell Migration and Invasion in Intrahepatic Cholangiocarcinoma via miR-92a-3p

by Tingming Liang, Lulu Shen, Yaya Ji, Lin Jia, Yuyang Dou and Li Guo

Genes 2021, 12(11), 1659; https://doi.org/10.3390/genes12111659 - 21 Oct 2021

Cited by 6 | Viewed by 1958

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a common type of human cancer with a poor prognosis, and investigating the potential molecular mechanisms that can contribute to gene diagnosis and therapy. Herein, based on the recently concerned vertebrate-specific Cyr61/CTGF/NOV (CCN) gene family because of its important roles in diverse diseases, we obtained NOV/CCN3 to query for its potential roles in tumorigenesis via bioinformatics analysis. Experimental validations confirmed that both NOV mRNA and protein are up-regulated in two ICC cell lines, suggesting that it may promote cell migration and invasion by promoting EMT. To elucidate the detailed regulatory mechanism, miR-92a-3p is screened and identified as a negative regulatory small RNA targeting NOV, and further experimental validation demonstrates that miR-92a-3p contributes to NOV-mediated migration and invasion of ICC via the Notch signaling pathway. Our study reveals that NOV may be a potential target for diagnosing and treating ICC, which will provide experimental data and molecular theoretical foundation for cancer treatment, particularly for future precision medicine. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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17 pages, 3255 KiB

Open AccessArticle

Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer

by Eleni Anastasiadou, Elena Messina, Tiziana Sanavia, Vittorio Labruna, Simona Ceccarelli, Francesca Megiorni, Giulia Gerini, Paola Pontecorvi, Simona Camero, Giorgia Perniola, Mary Anna Venneri, Pankaj Trivedi, Andrea Lenzi and Cinzia Marchese

Genes 2021, 12(9), 1400; https://doi.org/10.3390/genes12091400 - 10 Sep 2021

Cited by 5 | Viewed by 2089

Abstract

Epithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master regulator of oncogenes or tumor suppressors. To investigate novel miR-200c-3p target genes involved in EOC tumorigenesis, we evaluated the association between this miRNA and the mRNA expression of several potential target genes by RNA-seq data of both 46 EOC cell lines from Cancer Cell line Encyclopedia (CCLE) and 456 EOC patient bio-specimens from The Cancer Genome Atlas (TCGA). Both analyses showed a significant anticorrelation between miR-200c-3p and the protein phosphatase 3 catalytic subunit γ of calcineurin (PPP3CC) levels involved in the apoptosis pathway. Quantitative mRNA expression analysis in patient biopsies confirmed the inverse correlation between miR-200c-3p and PPP3CC levels. In vitro regulation of PPP3CC expression through miR-200c-3p and RNA interference technology led to a concomitant modulation of BCL2- and p-AKT-related pathways, suggesting the tumor suppressive role of PPP3CC in EOC. Our results suggest that inhibition of high expression of miR-200c-3p in EOC might lead to overexpression of the tumor suppressor PPP3CC and subsequent induction of apoptosis in EOC patients. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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14 pages, 5043 KiB

Open AccessArticle

miR-542-3p Contributes to the HK2-Mediated High Glycolytic Phenotype in Human Glioma Cells

by Junhyung Kim, Min Woo Park, Young Joon Park, Ju Won Ahn, Jeong Min Sim, Suwan Kim, Jinhyung Heo, Ji Hun Jeong, Mihye Lee, Jaejoon Lim and Jong-Seok Moon

Genes 2021, 12(5), 633; https://doi.org/10.3390/genes12050633 - 23 Apr 2021

Cited by 10 | Viewed by 3418

Abstract

(1) Background: The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear; (2) Methods: We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis; (3) Results: We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database; (4) Conclusions: miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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13 pages, 1965 KiB

Open AccessArticle

Expression of Estrogen Receptor- and Progesterone Receptor-Regulating MicroRNAs in Breast Cancer

by Tatiana Kalinina, Vladislav Kononchuk, Efim Alekseenok, Darya Obukhova, Sergey Sidorov, Dmitry Strunkin and Lyudmila Gulyaeva

Genes 2021, 12(4), 582; https://doi.org/10.3390/genes12040582 - 16 Apr 2021

Cited by 8 | Viewed by 2660

Abstract

In ~70% of breast cancer (BC) cases, estrogen and progesterone receptors (ER and PR) are overexpressed, which can change during tumor progression. Expression changes of these receptors during cancer initiation and progression can be caused by alterations in microRNA (miR, miRNA) expression. To assess the association of BC progression with aberrant expression of miRNAs that target ER and PR mRNAs, we quantified miR-19b, -222, -22, -378a, and -181a in BC samples (n = 174) by real-time PCR. Underexpression of miR-222 and miR-378a in stage T2–T4 BC was characteristic for HER2-overexpressing tumors. In addition, the expression of miR-181a and miR-378a was higher in these tumors than in tumors with a HER2 IHC score of 0 or 1+. In tumors with a Ki-67 index ≥ 14%, all tested miRNAs were underexpressed in BC with a high Allred PR score (6–8). In ER-and-PR–negative tumors, miR-22, miR-222, miR-181a, and miR-378a underexpression was associated with Ki-67 index > 35% (median value). MiR-19b and miR-22 underexpression could be a marker of lymph node metastasis in ER- and/or PR-positive tumors with HER2 IHC score 0. Thus, the association of miR-19b, miR-22, miR-222, miR-378a, and miR-181a levels with BC characteristics is influenced by the status of tumor ER, PR, HER2, and Ki-67. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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19 pages, 14743 KiB

Open AccessArticle

Clinical Identification of Dysregulated Circulating microRNAs and Their Implication in Drug Response in Triple Negative Breast Cancer (TNBC) by Target Gene Network and Meta-Analysis

by Amal Qattan, Taher Al-Tweigeri, Wafa Alkhayal, Kausar Suleman, Asma Tulbah and Suad Amer

Genes 2021, 12(4), 549; https://doi.org/10.3390/genes12040549 - 09 Apr 2021

Cited by 19 | Viewed by 3923

Abstract

Resistance to therapy is a persistent problem that leads to mortality in breast cancer, particularly triple-negative breast cancer (TNBC). MiRNAs have become a focus of investigation as tissue-specific regulators of gene networks related to drug resistance. Circulating miRNAs are readily accessible non-invasive potential biomarkers for TNBC diagnosis, prognosis, and drug-response. Our aim was to use systems biology, meta-analysis, and network approaches to delineate the drug resistance pathways and clinical outcomes associated with circulating miRNAs in TNBC patients. MiRNA expression analysis was used to investigate differentially regulated circulating miRNAs in TNBC patients, and integrated pathway regulation, gene ontology, and pharmacogenomic network analyses were used to identify target genes, miRNAs, and drug interaction networks. Herein, we identified significant differentially expressed circulating miRNAs in TNBC patients (miR-19a/b-3p, miR-25-3p, miR-22-3p, miR-210-3p, miR-93-5p, and miR-199a-3p) that regulate several molecular pathways (PAM (PI3K/Akt/mTOR), HIF-1, TNF, FoxO, Wnt, and JAK/STAT, PD-1/PD-L1 pathways and EGFR tyrosine kinase inhibitor resistance (TKIs)) involved in drug resistance. Through meta-analysis, we demonstrated an association of upregulated miR-93, miR-210, miR-19a, and miR-19b with poor overall survival outcomes in TNBC patients. These results identify miRNA-regulated mechanisms of drug resistance and potential targets for combination with chemotherapy to overcome drug resistance in TNBC. We demonstrate that integrated analysis of multi-dimensional data can unravel mechanisms of drug-resistance related to circulating miRNAs, particularly in TNBC. These circulating miRNAs may be useful as markers of drug response and resistance in the guidance of personalized medicine for TNBC. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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25 pages, 2028 KiB

Open AccessReview

Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology

by Edio Maldonado, Sebastian Morales-Pison, Fabiola Urbina, Lilian Jara and Aldo Solari

Genes 2022, 13(2), 234; https://doi.org/10.3390/genes13020234 - 26 Jan 2022

Cited by 5 | Viewed by 3338

Abstract

Transcriptional coactivators play a key role in RNA polymerase II transcription and gene regulation. One of the most important transcriptional coactivators is the Mediator (MED) complex, which is an evolutionary conserved large multiprotein complex. MED transduces the signal between DNA-bound transcriptional activators (gene-specific transcription factors) to the RNA polymerase II transcription machinery to activate transcription. It is known that MED plays an essential role in ER-mediated gene expression mainly through the MED1 subunit, since estrogen receptor (ER) can interact with MED1 by specific protein–protein interactions; therefore, MED1 plays a fundamental role in ER-positive breast cancer (BC) etiology. Additionally, other MED subunits also play a role in BC etiology. On the other hand, microRNAs (miRNAs) are a family of small non-coding RNAs, which can regulate gene expression at the post-transcriptional level by binding in a sequence-specific fashion at the 3′ UTR of the messenger RNA. The miRNAs are also important factors that influence oncogenic signaling in BC by acting as both tumor suppressors and oncogenes. Moreover, miRNAs are involved in endocrine therapy resistance of BC, specifically to tamoxifen, a drug that is used to target ER signaling. In metazoans, very little is known about the transcriptional regulation of miRNA by the MED complex and less about the transcriptional regulation of miRNAs involved in BC initiation and progression. Recently, it has been shown that MED1 is able to regulate the transcription of the ER-dependent miR-191/425 cluster promoting BC cell proliferation and migration. In this review, we will discuss the role of MED1 transcriptional coactivator in the etiology of BC and in endocrine therapy-resistance of BC and also the contribution of other MED subunits to BC development, progression and metastasis. Lastly, we identified miRNAs that potentially can regulate the expression of MED subunits. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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21 pages, 1562 KiB

Open AccessReview

Emerging Role of isomiRs in Cancer: State of the Art and Recent Advances

by Veronica Zelli, Chiara Compagnoni, Roberta Capelli, Alessandra Corrente, Jessica Cornice, Davide Vecchiotti, Monica Di Padova, Francesca Zazzeroni, Edoardo Alesse and Alessandra Tessitore

Genes 2021, 12(9), 1447; https://doi.org/10.3390/genes12091447 - 20 Sep 2021

Cited by 10 | Viewed by 3586

Abstract

The advent of Next Generation Sequencing technologies brought with it the discovery of several microRNA (miRNA) variants of heterogeneous lengths and/or sequences. Initially ascribed to sequencing errors/artifacts, these isoforms, named isomiRs, are now considered non-canonical variants that originate from physiological processes affecting the canonical miRNA biogenesis. To date, accurate IsomiRs abundance, biological activity, and functions are not completely understood; however, the study of isomiR biology is an area of great interest due to their high frequency in the human miRNome, their putative functions in cooperating with the canonical miRNAs, and potential for exhibiting novel functional roles. The discovery of isomiRs highlighted the complexity of the small RNA transcriptional landscape in several diseases, including cancer. In this field, the study of isomiRs could provide further insights into the miRNA biology and its implication in oncogenesis, possibly providing putative new cancer diagnostic, prognostic, and predictive biomarkers as well. In this review, a comprehensive overview of the state of research on isomiRs in different cancer types, including the most common tumors such as breast cancer, colorectal cancer, melanoma, and prostate cancer, as well as in the less frequent tumors, as for example brain tumors and hematological malignancies, will be summarized and discussed. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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14 pages, 977 KiB

Open AccessReview

SALL4 and microRNA: The Role of Let-7

by Jun Liu, Madeline A. Sauer, Shaza G. Hussein, Junyu Yang, Daniel G. Tenen and Li Chai

Genes 2021, 12(9), 1301; https://doi.org/10.3390/genes12091301 - 24 Aug 2021

Cited by 6 | Viewed by 2800

Abstract

SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regarding how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as important regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize current knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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13 pages, 571 KiB

Open AccessEditor’s ChoiceReview

MiRNAs and Cancer: Key Link in Diagnosis and Therapy

by Yu Shi, Zihao Liu, Qun Lin, Qing Luo, Yinghuan Cen, Juanmei Li, Xiaolin Fang and Chang Gong

Genes 2021, 12(8), 1289; https://doi.org/10.3390/genes12081289 - 23 Aug 2021

Cited by 51 | Viewed by 4246

Abstract

Since the discovery of the first microRNA (miRNA), the exploration of miRNA biology has come to a new era in recent decades. Monumental studies have proven that miRNAs can be dysregulated in different types of cancers and the roles of miRNAs turn out to function to either tumor promoters or tumor suppressors. The interplay between miRNAs and the development of cancers has grabbed attention of miRNAs as novel tools and targets for therapeutic attempts. Moreover, the development of miRNA delivery system accelerates miRNA preclinical implications. In this review, we depict recent advances of miRNAs in cancer and discuss the potential diagnostic or therapeutic approaches of miRNAs. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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13 pages, 322 KiB

Open AccessReview

Association of Exosomal miR-210 with Signaling Pathways Implicated in Lung Cancer

by Qiaoyi Chen and Xiaoge Xie

Genes 2021, 12(8), 1248; https://doi.org/10.3390/genes12081248 - 16 Aug 2021

Cited by 7 | Viewed by 3095

Abstract

MicroRNA is a class of non-coding RNA involved in post-transcriptional gene regulation. Aberrant expression of miRNAs is well-documented in molecular cancer biology. Extensive research has shown that miR-210 is implicated in the progression of multiple cancers including that of the lung, bladder, colon, and renal cell carcinoma. In recent years, exosomes have been evidenced to facilitate cell–cell communication and signaling through packaging and transporting active biomolecules such as miRNAs and thereby modify the cellular microenvironment favorable for lung cancers. MiRNAs encapsulated inside the lipid bilayer of exosomes are stabilized and transmitted to target cells to exert alterations in the epigenetic landscape. The currently available literature indicates that exosomal miR-210 is involved in the regulation of various lung cancer-related signaling molecules and pathways, including STAT3, TIMP-1, KRAS/BACH2/GATA-3/RIP3, and PI3K/AKT. Here, we highlight major findings and progress on the roles of exosomal miR-210 in lung cancer. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

20 pages, 382 KiB

Open AccessReview

Circulating microRNAs from the Molecular Mechanisms to Clinical Biomarkers: A Focus on the Clear Cell Renal Cell Carcinoma

by Claudia Tito, Elena De Falco, Paolo Rosa, Alessia Iaiza, Francesco Fazi, Vincenzo Petrozza and Antonella Calogero

Genes 2021, 12(8), 1154; https://doi.org/10.3390/genes12081154 - 28 Jul 2021

Cited by 14 | Viewed by 1803

Abstract

microRNAs (miRNAs) are emerging as relevant molecules in cancer development and progression. MiRNAs add a post-transcriptional level of control to the regulation of gene expression. The deregulation of miRNA expression results in changing the molecular circuitry in which miRNAs are involved, leading to alterations of cell fate determination. In this review, we describe the miRNAs that are emerging as innovative molecular biomarkers from liquid biopsies, not only for diagnosis, but also for post-surgery management in cancer. We focus our attention on renal cell carcinoma, in particular highlighting the crucial role of circulating miRNAs in clear cell renal cell carcinoma (ccRCC) management. In addition, the functional deregulation of miRNA expression in ccRCC is also discussed, to underline the contribution of miRNAs to ccRCC development and progression, which may be relevant for the identification and design of innovative clinical strategies against this tumor. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

11 pages, 276 KiB

Open AccessReview

MicroRNA Changes in Gastric Carcinogenesis: Differential Dysregulation during Helicobacter pylori and EBV Infection

by Christian Prinz, Kemal Mese and David Weber

Genes 2021, 12(4), 597; https://doi.org/10.3390/genes12040597 - 19 Apr 2021

Cited by 8 | Viewed by 2425

Abstract

Despite medical advances, gastric-cancer (GC) mortality remains high in Europe. Bacterial infection with Helicobacter pylori (H. pylori) and viral infection with the Epstein–Barr virus (EBV) are associated with the development of both distal and proximal gastric cancer. Therefore, the detection of these infections and the prediction of further cancer development could be clinically significant. To this end, microRNAs (miRNAs) could serve as promising new tools. MiRNAs are highly conserved noncoding RNAs that play an important role in gene silencing, mainly acting via translational repression and the degradation of mRNA targets. Recent reports demonstrate the downregulation of numerous miRNAs in GC, especially miR-22, miR-145, miR-206, miR-375, and miR-490, and these changes seem to promote cancer-cell invasion and tumor spreading. The dysregulation of miR-106b, miR-146a, miR-155, and the Let-7b/c complex seems to be of particular importance during H. pylori infection or gastric carcinogenesis. In contrast, many reports describe changes in host miRNA expression and outline the effects of bamHI-A region rightward transcript (BART) miRNA in EBV-infected tissue. The differential regulation of these miRNA, acting alone or in close interaction when both infections coexist, may therefore enable us to detect cancer earlier. In this review, we focus on the two different etiologies of gastric cancer and outline the molecular pathways through which H. pylori- or EBV-induced changes might synergistically act via miR-155 dysregulation to potentiate cancer risk. The three markers, namely, H. pylori presence, EBV infection, and miR-155 expression, may be checked in routine biopsies to evaluate the risk of developing gastric cancer. Full article

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