Next Issue
Volume 10, February
Previous Issue
Volume 9, October
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.6
4.3
Journals
ncRNA
Volume 9
Issue 6
share announcement

Non-Coding RNA, Volume 9, Issue 6 (December 2023) – 13 articles

Cover Story (view full-size image): The expression of the TGFb family member NODAL has been correlated with the plasticity and invasiveness of tumour cells, but its implication in melanoma is controversial. A targeted deletion of NODAL exon2 in melanoma cells is now shown to impair their ability to form tumours and to colonize distant tissues. However, this phenotype does not result from the absence of NODAL, but from the disabled expression of a natural antisense transcript of NODAL, now called LADON. LADON transcripts are packaged in secreted exosomes and, through their differential impact on the expression of oncogenes and tumour suppressors, they promote the mesenchymal to amoeboid transition that is key to tumour progression in melanoma. These findings raise the question of LADON’s implication in other types of cancer. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
6 pages, 239 KiB  
Editorial
The Non-Coding RNA Journal Club: Highlights on Recent Papers—13
by Patrick K. T. Shiu, Johanna K. DiStefano, Suresh K. Alahari, Francisco J. Enguita, Mark W. Feinberg, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Diana Luna Buitrago, Andrea Caporali, Alessandro Mannucci and Ajay Goel
Non-Coding RNA 2023, 9(6), 76; https://doi.org/10.3390/ncrna9060076 - 14 Dec 2023
Viewed by 1356
Abstract
We are delighted to share with you our thirteenth Journal Club and highlight some of the most interesting papers published recently [...] Full article
(This article belongs to the Collection The Non-Coding RNA Journal Club: Highlights on Recent Papers)
14 pages, 964 KiB  
Review
Regulation of Macrophage Polarization in Allergy by Noncoding RNAs
by Osamu Ishibashi, Stefan A. Muljo and Zohirul Islam
Non-Coding RNA 2023, 9(6), 75; https://doi.org/10.3390/ncrna9060075 - 11 Dec 2023
Viewed by 2193
Abstract
Allergy is a type 2 immune reaction triggered by antigens known as allergens, including food and environmental substances such as peanuts, plant pollen, fungal spores, and the feces and debris of mites and insects. Macrophages are myeloid immune cells with phagocytic abilities that [...] Read more.
Allergy is a type 2 immune reaction triggered by antigens known as allergens, including food and environmental substances such as peanuts, plant pollen, fungal spores, and the feces and debris of mites and insects. Macrophages are myeloid immune cells with phagocytic abilities that process exogenous and endogenous antigens. Upon activation, they can produce effector molecules such as cytokines as well as anti-inflammatory molecules. The dysregulation of macrophage function can lead to excessive type 1 inflammation as well as type 2 inflammation, which includes allergic reactions. Thus, it is important to better understand how macrophages are regulated in the pathogenesis of allergies. Emerging evidence highlights the role of noncoding RNAs (ncRNAs) in macrophage polarization, which in turn can modify the pathogenesis of various immune-mediated diseases, including allergies. This review summarizes the current knowledge regarding this topic and considers three classes of ncRNAs: microRNAs, long ncRNAs, and circular ncRNAs. Understanding the roles of these ncRNAs in macrophage polarization will provide new insights into the pathogenesis of allergies and identify potential novel therapeutic targets. Full article
(This article belongs to the Special Issue Non-Coding RNA in the Immune System)
►▼ Show Figures

Figure 1

19 pages, 3509 KiB  
Article
Age and 17β-Estradiol (E2) Facilitate Nuclear Export and Argonaute Loading of microRNAs in the Female Brain
by Megan L. Linscott, Yoldas Yildiz, Sarah Flury, Mikayla L. Newby and Toni R. Pak
Non-Coding RNA 2023, 9(6), 74; https://doi.org/10.3390/ncrna9060074 - 06 Dec 2023
Cited by 1 | Viewed by 1716
Abstract
Aging in women is accompanied by a dramatic change in circulating sex steroid hormones. Specifically, the primary circulating estrogen, 17β-estradiol (E2), is nearly undetectable in post-menopausal women. This decline is associated with a variety of cognitive and mood disorders, yet hormone [...] Read more.
Aging in women is accompanied by a dramatic change in circulating sex steroid hormones. Specifically, the primary circulating estrogen, 17β-estradiol (E2), is nearly undetectable in post-menopausal women. This decline is associated with a variety of cognitive and mood disorders, yet hormone replacement therapy is only effective within a narrow window of time surrounding the menopausal transition. Our previous work identified microRNAs as a potential molecular substrate underlying the change in E2 efficacy associated with menopause in advanced age. Specifically, we showed that E2 regulated a small subset of mature miRNAs in the aging female brain. In this study, we hypothesized that E2 regulates the stability of mature miRNAs by altering their subcellular localization and their association with argonaute proteins. We also tested the hypothesis that the RNA binding protein, hnRNP A1, was an important regulator of mature miR-9-5p expression in neuronal cells. Our results demonstrated that E2 treatment affected miRNA subcellular localization and its association with argonaute proteins differently, depending on the length of time following E2 deprivation (i.e., ovariectomy). We also provide strong evidence that hnRNP A1 regulates the transcription of pri-miR-9 and likely plays a posttranscriptional role in mature miR-9-5p turnover. Taken together, these data have important implications for considering the optimal timing for hormone replacement therapy, which might be less dependent on age and more related to how long treatment is delayed following menopause. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
►▼ Show Figures

Figure 1

14 pages, 1773 KiB  
Article
MicroRNAs in Gingival Crevicular Fluid: An Observational Case-Control Study of Differential Expression in Periodontitis
by Pedro J. Almiñana-Pastor, Francisco M. Alpiste-Illueca, Pablo Micó-Martinez, Jose Luis García-Giménez, Eva García-López and Andrés López-Roldán
Non-Coding RNA 2023, 9(6), 73; https://doi.org/10.3390/ncrna9060073 - 18 Nov 2023
Cited by 1 | Viewed by 1740
Abstract
Objectives: microRNAs (miRNAs) present in the gingival crevicular fluid (GCF) of patients with chronic periodontitis may serve as biomarkers of periodontal disease. The aim of this study was to perform a miRNA-sequencing study of all miRNAs present in GCF, comparing miRNA expression level [...] Read more.
Objectives: microRNAs (miRNAs) present in the gingival crevicular fluid (GCF) of patients with chronic periodontitis may serve as biomarkers of periodontal disease. The aim of this study was to perform a miRNA-sequencing study of all miRNAs present in GCF, comparing miRNA expression level profiles between advanced chronic periodontitis (CP) patients and healthy subjects (HS). Materials and methods: GCF samples were collected from the single-rooted teeth of patients with severe CP (n = 11) and of HS (n = 12). miRNAs were isolated from GCF using an miRNeasy Serum/Plasma kit(Qiagen GmbH, Hilden, Germany). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression levels of miRNA candidates involved in periodontal pathogenesis. Results: Of all the sequenced miRNAs, miR-199, miR-146a, miR-30a, and miR-338 were identified as best representing the CP patient samples. The validation study identified miR-199 as the most powerful biomarker used to define periodontitis. Conclusions: Upon sequencing all known miRNAs in GCF for the first time, we uncovered several potential biomarkers to define periodontitis. Identifying miRNAS in the GCF using high-throughput approaches will clarify the role of these molecules in periodontitis and provide biomarkers with potential applications. Full article
►▼ Show Figures

Figure 1

14 pages, 2176 KiB  
Article
Ethanol- and PARP-Mediated Regulation of Ribosome-Associated Long Non-Coding RNA (lncRNA) in Pyramidal Neurons
by Hooriyah S. Rizavi, Hannah E. Gavin, Harish R. Krishnan, David P. Gavin and Rajiv P. Sharma
Non-Coding RNA 2023, 9(6), 72; https://doi.org/10.3390/ncrna9060072 - 17 Nov 2023
Viewed by 1361
Abstract
Although, by definition, long noncoding RNAs (lncRNAs) are not translated, they are sometimes associated with ribosomes. In fact, some estimates suggest the existence of more than 50 K lncRNA molecules that could encode for small peptides. We examined the effects of an ethanol [...] Read more.
Although, by definition, long noncoding RNAs (lncRNAs) are not translated, they are sometimes associated with ribosomes. In fact, some estimates suggest the existence of more than 50 K lncRNA molecules that could encode for small peptides. We examined the effects of an ethanol and Poly-ADP Ribose Polymerase (PARP) inhibitor (ABT-888) on ribosome-bound lncRNAs. Mice were administered via intraperitoneal injection (i.p.) either normal saline (CTL) or ethanol (EtOH) twice a day for four consecutive days. On the fourth day, a sub-group of mice administered with ethanol also received ABT-888 (EtOH+ABT). Ribosome-bound lncRNAs in CaMKIIα-expressing pyramidal neurons were measured using the Translating Ribosome Affinity Purification (TRAP) technique. Our findings show that EtOH altered the attachment of 107 lncRNA transcripts, while EtOH+ABT altered 60 lncRNAs. Among these 60 lncRNAs, 49 were altered by both conditions, while EtOH+ABT uniquely altered the attachment of 11 lncRNA transcripts that EtOH alone did not affect. To validate these results, we selected eight lncRNAs (Mir124-2hg, 5430416N02Rik, Snhg17, Snhg12, Snhg1, Mir9-3hg, Gas5, and 1110038B12Rik) for qRT-PCR analysis. The current study demonstrates that ethanol-induced changes in lncRNA attachment to ribosomes can be mitigated by the addition of the PARP inhibitor ABT-888. Full article
►▼ Show Figures

Figure 1

19 pages, 1799 KiB  
Article
LADON, a Natural Antisense Transcript of NODAL, Promotes Tumour Progression and Metastasis in Melanoma
by Annie Dutriaux, Serena Diazzi, Chiara Bresesti, Sylvie Hardouin, Frédérique Deshayes, Jérôme Collignon and Domenico Flagiello
Non-Coding RNA 2023, 9(6), 71; https://doi.org/10.3390/ncrna9060071 - 15 Nov 2023
Viewed by 1980
Abstract
The TGFβ family member NODAL, repeatedly required during embryonic development, has also been associated with tumour progression. Our aim was to clarify the controversy surrounding its involvement in melanoma tumour progression. We found that the deletion of the NODAL exon 2 in a [...] Read more.
The TGFβ family member NODAL, repeatedly required during embryonic development, has also been associated with tumour progression. Our aim was to clarify the controversy surrounding its involvement in melanoma tumour progression. We found that the deletion of the NODAL exon 2 in a metastatic melanoma cell line impairs its ability to form tumours and colonize distant tissues. However, we show that this phenotype does not result from the absence of NODAL, but from a defect in the expression of a natural antisense transcript of NODAL, here called LADON. We show that LADON expression is specifically activated in metastatic melanoma cell lines, that its transcript is packaged in exosomes secreted by melanoma cells, and that, via its differential impact on the expression of oncogenes and tumour suppressors, it promotes the mesenchymal to amoeboid transition that is critical for melanoma cell invasiveness. LADON is, therefore, a new player in the regulatory network governing tumour progression in melanoma and possibly in other types of cancer. Full article
(This article belongs to the Special Issue The Importance of Non-coding RNAs in Epithelial Cancers)
►▼ Show Figures

Figure 1

23 pages, 1544 KiB  
Review
An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer
by Moises Martinez-Castillo, Abdelrahman M. Elsayed, Gabriel López-Berestein, Paola Amero and Cristian Rodríguez-Aguayo
Non-Coding RNA 2023, 9(6), 70; https://doi.org/10.3390/ncrna9060070 - 11 Nov 2023
Cited by 1 | Viewed by 1623
Abstract
Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for [...] Read more.
Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field with substantial clinical implications. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
►▼ Show Figures

Figure 1

18 pages, 761 KiB  
Article
The Typical tRNA Co-Expresses Multiple 5′ tRNA Halves Whose Sequences and Abundances Depend on Isodecoder and Isoacceptor and Change with Tissue Type, Cell Type, and Disease
by Robert Brian Akins, Kayleigh Ostberg, Tess Cherlin, Nikolas J. Tsiouplis, Phillipe Loher and Isidore Rigoutsos
Non-Coding RNA 2023, 9(6), 69; https://doi.org/10.3390/ncrna9060069 - 06 Nov 2023
Cited by 1 | Viewed by 2098
Abstract
Transfer RNA-derived fragments (tRFs) are noncoding RNAs that arise from either mature transfer RNAs (tRNAs) or their precursors. One important category of tRFs comprises the tRNA halves, which are generated through cleavage at the anticodon. A given tRNA typically gives rise to several [...] Read more.
Transfer RNA-derived fragments (tRFs) are noncoding RNAs that arise from either mature transfer RNAs (tRNAs) or their precursors. One important category of tRFs comprises the tRNA halves, which are generated through cleavage at the anticodon. A given tRNA typically gives rise to several co-expressed 5’-tRNA halves (5′-tRHs) that differ in the location of their 3′ ends. These 5′-tRHs, even though distinct, have traditionally been treated as indistinguishable from one another due to their near-identical sequences and lengths. We focused on co-expressed 5′-tRHs that arise from the same tRNA and systematically examined their exact sequences and abundances across 10 different human tissues. To this end, we manually curated and analyzed several hundred human RNA-seq datasets from NCBI’s Sequence Run Archive (SRA). We grouped datasets from the same tissue into their own collection and examined each group separately. We found that a given tRNA produces different groups of co-expressed 5′-tRHs in different tissues, different cell lines, and different diseases. Importantly, the co-expressed 5′-tRHs differ in their sequences, absolute abundances, and relative abundances, even among tRNAs with near-identical sequences from the same isodecoder or isoacceptor group. The findings suggest that co-expressed 5′-tRHs that are produced from the same tRNA or closely related tRNAs have distinct, context-dependent roles. Moreover, our analyses show that cell lines modeling the same tissue type and disease may not be interchangeable when it comes to experimenting with tRFs. Full article
(This article belongs to the Special Issue Small RNAs – Big Roles: IsomiRs, tRNA Fragments, and rRNA Fragments in Human Health and Disease)
►▼ Show Figures

Figure 1

30 pages, 37976 KiB  
Review
Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma
by Nor Hayati Ismail, Ali Mussa, Mutaz Jamal Al-Khreisat, Shafini Mohamed Yusoff, Azlan Husin, Hamid Ali Nagi Al-Jamal, Muhammad Farid Johan and Md Asiful Islam
Non-Coding RNA 2023, 9(6), 68; https://doi.org/10.3390/ncrna9060068 - 03 Nov 2023
Cited by 2 | Viewed by 1897
Abstract
The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs [...] Read more.
The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs can serve as oncogenes or tumor suppressors depending on the target genes. In MM, miRNA disruption could result in abnormal gene expression responsible for cell growth, apoptosis, and other biological processes pertinent to cancer development. The dysregulated miRNAs inhibit the activity of tumor suppressor genes, contributing to disease progression. Nonetheless, several miRNAs are downregulated in MM and have been identified as gene regulators implicated in extracellular matrix remodeling and cell adhesion. miRNA depletion potentially facilitates the tumor advancement and resistance of therapeutic drugs. Additionally, lncRNAs are key regulators of numerous cellular processes, such as gene expression, chromatin remodeling, protein trafficking, and recently linked MM development. The lncRNAs are uniquely expressed and influence gene expression that supports MM growth, in addition to facilitating cellular proliferation and viability via multiple molecular pathways. miRNA and lncRNA alterations potentially result in anomalous gene expression and interfere with the regular functioning of MM. Thus, this review aims to highlight the dysregulation of these ncRNAs, which engender novel therapeutic modalities for the treatment of MM. Full article
(This article belongs to the Special Issue Current Strategies to Investigate the Role of ncRNAs in Carcinogenesis)
►▼ Show Figures

Figure 1

12 pages, 1639 KiB  
Article
Downregulation of Exosomal hsa-miR-551b-3p in Obesity and Its Link to Type 2 Diabetes Mellitus
by Kseniia V. Dracheva, Irina A. Pobozheva, Kristina A. Anisimova, Stanislav G. Balandov, Maria N. Grunina, Zarina M. Hamid, Dmitriy I. Vasilevsky, Sofya N. Pchelina and Valentina V. Miroshnikova
Non-Coding RNA 2023, 9(6), 67; https://doi.org/10.3390/ncrna9060067 - 02 Nov 2023
Cited by 2 | Viewed by 1367
Abstract
Obesity is a significant risk factor for the development of type 2 diabetes mellitus (T2DM). Adipose tissue dysfunction can affect the pool of circulating exosomal miRNAs, driving concomitant disease in obesity. These exosomal miRNAs can reflect adipose tissue functionality, thus serving as prognostic [...] Read more.
Obesity is a significant risk factor for the development of type 2 diabetes mellitus (T2DM). Adipose tissue dysfunction can affect the pool of circulating exosomal miRNAs, driving concomitant disease in obesity. These exosomal miRNAs can reflect adipose tissue functionality, thus serving as prognostic biomarkers for disease monitoring in case of T2DM. In the present study, we conducted NanoString microRNA profiling of extracellular vesicles (EVs) secreted by adipose tissue of obese patients (body mass index (BMI) > 35) without T2DM and nonobese individuals (BMI < 30) as a control group. Functional and pathway enrichment analysis showed that miRNAs associated with obesity in this study were implicated in insulin signaling and insulin resistance biological pathways. Further, these microRNAs were screened in serum EVs in the following groups: (1) obese patients with T2DM, (2) obese patients without T2DM, and (3) nonobese individuals as a control group. has-miR-551b-3p was shown to be downregulated in adipose tissue EVs, as well as in serum EVs, of patients with obesity without T2DM. At the same time, the serum exosomal hsa-miR-551b-3p content was significantly higher in obese patients with T2DM when compared with obese patients without T2DM and may be a potential biomarker of T2DM development in obesity. Full article
(This article belongs to the Special Issue Non-coding RNA and Diabetes 2.0)
►▼ Show Figures

Graphical abstract

28 pages, 7143 KiB  
Article
Organotypic 3D Cell-Architecture Impacts the Expression Pattern of miRNAs–mRNAs Network in Breast Cancer SKBR3 Cells
by María de los Ángeles Gastélum-López, Maribel Aguilar-Medina, Cristina García Mata, Jorge López-Gutiérrez, Geovanni Romero-Quintana, Mercedes Bermúdez, Mariana Avendaño-Felix, César López-Camarillo, Carlos Pérez-Plascencia, Adriana S Beltrán and Rosalío Ramos-Payán
Non-Coding RNA 2023, 9(6), 66; https://doi.org/10.3390/ncrna9060066 - 26 Oct 2023
Viewed by 1908
Abstract
Background. Currently, most of the research on breast cancer has been carried out in conventional two-dimensional (2D) cell cultures due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell–cell [...] Read more.
Background. Currently, most of the research on breast cancer has been carried out in conventional two-dimensional (2D) cell cultures due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell–cell and cell–extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. Methods. In this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differentially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. Results. We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2 × 105 μm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both miRNAs, and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene ontology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cytoskeleton organization, as well as in the MAPK and AGE–RAGE signaling KEGG-pathways. Interestingly, hsa-mir-122-5p (Fold Change (FC) = 15.4), hsa-mir-369-3p (FC = 11.4), and hsa-mir-10b-5p (FC = 20.1) regulated up to 81% of the 70 downregulated DE-mRNAs. Conclusion. The organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of the miRNAs–mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell–cell and cell–ECM as well as the change in the culture architecture impacts gene expression, and, therefore, support the pertinence of migrating breast cancer research from conventional cultures to 3D models. Full article
(This article belongs to the Topic Non-coding RNAs in Cancer: Markers in Disease Progression and Therapy)
►▼ Show Figures

Figure 1

16 pages, 3000 KiB  
Article
Discovery of Novel miRNAs in Colorectal Cancer: Potential Biological Roles and Clinical Utility
by Iael Weissberg Minutentag, Ana Laura Seneda, Mateus C. Barros-Filhos, Márcio de Carvalho, Vanessa G. P. Souza, Claudia N. Hasimoto, Marcelo P. T. Moraes, Fabio A. Marchi, Wan L. Lam, Patricia P. Reis and Sandra A. Drigo
Non-Coding RNA 2023, 9(6), 65; https://doi.org/10.3390/ncrna9060065 - 26 Oct 2023
Viewed by 1757
Abstract
Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO [...] Read more.
Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO data (discovery and validation groups). We used TCGA data from five tissues to analyze miRNA tissue specificity. miRDB was used to predict miRNA targets, and the UCSC Xena Browser was used to evaluate target expression. After successive analyses, we identified 15 novel miRNAs with the same expression patterns in CRC in both the discovery and validation groups. Four molecules (nov-miR-13844-5p, nov-miR-7154-5p, nov-miR-5035-3p, and nov-miR-590-5p) were differentially expressed in proximal and distal CRC. The nov-miR-3345-5p and nov-miR-13172-3p, which are upregulated in tumors, are only expressed in colorectal tissues. These molecules have been linked to a worse prognosis in right-sided colon and rectal carcinomas. An analysis revealed an association between eight novel miRNAs and 81 targets, mostly cancer-related genes, with varying expression based on tumor location. These findings provide new miRNAs with potential biological relevance, molecular biomarkers, and therapeutic targets for CRC treatment. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Clinical Implications of Non-coding RNAs in Cancer)
►▼ Show Figures

Graphical abstract

19 pages, 1764 KiB  
Article
A Machine Learning Model Based on microRNAs for the Diagnosis of Essential Hypertension
by Amela Jusic, Inela Junuzovic, Ahmed Hujdurovic, Lu Zhang, Mélanie Vausort and Yvan Devaux
Non-Coding RNA 2023, 9(6), 64; https://doi.org/10.3390/ncrna9060064 - 25 Oct 2023
Viewed by 1796
Abstract
Introduction: Hypertension is a major and modifiable risk factor for cardiovascular diseases. Essential, primary, or idiopathic hypertension accounts for 90–95% of all cases. Identifying novel biomarkers specific to essential hypertension may help in understanding pathophysiological pathways and developing personalized treatments. We tested whether [...] Read more.
Introduction: Hypertension is a major and modifiable risk factor for cardiovascular diseases. Essential, primary, or idiopathic hypertension accounts for 90–95% of all cases. Identifying novel biomarkers specific to essential hypertension may help in understanding pathophysiological pathways and developing personalized treatments. We tested whether the integration of circulating microRNAs (miRNAs) and clinical risk factors via machine learning modeling may provide useful information and novel tools for essential hypertension diagnosis and management. Materials and methods: In total, 174 participants were enrolled in the present observational case–control study, among which, there were 89 patients with essential hypertension and 85 controls. A discovery phase was conducted using small RNA sequencing in whole blood samples obtained from age- and sex-matched hypertension patients (n = 30) and controls (n = 30). A validation phase using RT-qPCR involved the remaining 114 participants. For machine learning, 170 participants with complete data were used to generate and evaluate the classification model. Results: Small RNA sequencing identified seven miRNAs downregulated in hypertensive patients as compared with controls in the discovery group, of which six were confirmed with RT-qPCR. In the validation group, miR-210-3p/361-3p/362-5p/378a-5p/501-5p were also downregulated in hypertensive patients. A machine learning support vector machine (SVM) model including clinical risk factors (sex, BMI, alcohol use, current smoker, and hypertension family history), miR-361-3p, and miR-501-5p was able to classify hypertension patients in a test dataset with an AUC of 0.90, a balanced accuracy of 0.87, a sensitivity of 0.83, and a specificity of 0.91. While five miRNAs exhibited substantial downregulation in hypertension patients, only miR-361-3p and miR-501-5p, alongside clinical risk factors, were consistently chosen in at least eight out of ten sub-training sets within the SVM model. Conclusions: This study highlights the potential significance of miRNA-based biomarkers in deepening our understanding of hypertension’s pathophysiology and in personalizing treatment strategies. The strong performance of the SVM model highlights its potential as a valuable asset for diagnosing and managing essential hypertension. The model remains to be extensively validated in independent patient cohorts before evaluating its added value in a clinical setting. Full article
(This article belongs to the Collection Regulatory RNAs in Cardiovascular Development and Disease)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-13
Previous Issue
Next Issue
Back to TopTop