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Biomolecules
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The Role of Non-Coding RNAs in Health and Disease
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The Role of Non-Coding RNAs in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 4259

Special Issue Editor

Dr. Narasimman Gurusamy

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA
Interests: non-coding RNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Non-coding RNAs have emerged as pivotal molecular regulators in numerous biological processes, fundamentally altering our understanding of the complexities within the central dogma of biology. This Special Issue, “Non-Coding RNAs in Health and Disease”, aims to explore the multifaceted roles of non-coding RNAs, encompassing microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and others, in orchestrating cellular functions, disease progression, and the maintenance of health. The collection of articles, reviews, and research papers presented in this issue delves into the latest discoveries and innovative approaches in non-coding RNA research, highlighting their significance in gene expression regulation, epigenetic modifications, and their potential as therapeutic targets and diagnostic biomarkers.

This Special Issue will provide insightful analyses on the mechanisms by which non-coding RNAs influence disease pathogenesis, including cancer, neurodegenerative disorders, cardiovascular diseases, and more, offering a comprehensive overview of the current state of knowledge in the field. Additionally, this issue will explore the therapeutic potential of non-coding RNAs, examining the challenges and opportunities in harnessing these molecules for clinical applications. By bridging fundamental research and clinical practice, this Special Issue aims to accelerate the translation of non-coding RNA research into tangible health benefits, underscoring the importance of non-coding RNAs in the intricate landscape of health and disease.

Dr. Narasimman Gurusamy
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • non-coding RNA
  • microRNA (miRNA)
  • long noncoding RNA (lncRNA)
  • circular RNA (circRNA)
  • gene expression regulation
  • epigenetic modifications

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Published Papers (5 papers)

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Research

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16 pages, 7367 KiB  
Article
Mitochondrial miRNA miR-134-5p Play Oncogenic Role in Clear Cell Renal Cell Carcinoma
by Tao Shen, Wei Wang, Haiyang Wang, Xinyi Zhu and Guoping Zhu
Biomolecules 2025, 15(3), 445; https://doi.org/10.3390/biom15030445 - 20 Mar 2025
Viewed by 534
Abstract
Mitochondrial miRNAs (mitomiRs), which are miRNAs that located within mitochondria, have emerged as crucial regulators in a variety of human diseases, including multiple types of cancers. However, the specific role of mitomiRs in clear cell renal cell carcinoma (ccRCC) remains elusive. In this [...] Read more.
Mitochondrial miRNAs (mitomiRs), which are miRNAs that located within mitochondria, have emerged as crucial regulators in a variety of human diseases, including multiple types of cancers. However, the specific role of mitomiRs in clear cell renal cell carcinoma (ccRCC) remains elusive. In this study, we employed a combination of experimental and bioinformatic approaches to uncover the diverse and abundant subcellular distribution of miRNAs within mitochondria in ccRCC. Notably, RNA sequencing after mitochondrial fractionation identified miR-134-5p as a miRNA predominantly detected in the mitochondria of 786O cells, and its expression is significantly upregulated compared to that in 293T cells. Differential expression and survival analyses from TCGA reveal that the upregulation of miR-134-5p is prevalent and closely associated with poor survival outcomes in ccRCC patients. Functionally, exogenous overexpression of miR-134-5p mimics promotes migration in both 786O and Caki-1 cells. Mechanistically, overexpressing the miR-134-5p mimic dramatically downregulates the mRNA levels of CHST6, SFXN2, and GRIK3, whereas the miR-134-5p inhibitor markedly upregulates their expression. Notably, these target mRNAs also predominantly detected in the mitochondria of 786O cells. The downregulated expression signatures of CHST6, SFXN2, and GRIK3 are also closely correlated with poor survival outcomes in ccRCC patients. Taken together, our work identifies a novel mitomiR, miR-134-5p, in ccRCC, provides potential targets that could serve as effective biomarkers for ccRCC diagnosis and prognosis, and opens new avenues for understanding the mitomiR-directed regulatory network in ccRCC progression. Full article
(This article belongs to the Special Issue The Role of Non-Coding RNAs in Health and Disease)
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14 pages, 1292 KiB  
Article
Differential Expression of miR-223-3p and miR-26-5p According to Different Stages of Mastitis in Dairy Cows
by Eleonora Dall’Olio, Fabio De Rensis, Eugenio Martignani, Silvia Miretti, Ugo Ala, Valeria Cavalli, Claudio Cipolat-Gotet, Melania Andrani, Mario Baratta and Roberta Saleri
Biomolecules 2025, 15(2), 235; https://doi.org/10.3390/biom15020235 - 6 Feb 2025
Viewed by 819
Abstract
Mastitis is the leading cause of economic losses in dairy farming, significantly impairing animal welfare and the quality and quantity of milk production. MicroRNAs are increasingly gaining attention, in both human and veterinary medicine, as biomarkers for various diseases. This study evaluated the [...] Read more.
Mastitis is the leading cause of economic losses in dairy farming, significantly impairing animal welfare and the quality and quantity of milk production. MicroRNAs are increasingly gaining attention, in both human and veterinary medicine, as biomarkers for various diseases. This study evaluated the diagnostic potential of four circulating microRNAs (miR-26-5p, miR-142-5p, miR-146a, and miR-223-3p) by examining changes in their expression in milk samples from dairy cows at different immune-cell subpopulations correlated to different stage of mastitis with a validated method. Additionally, this study has analyzed the possible source of these circulating microRNAs by the measurement of their secretion from activated immune cells (lymphocytes, monocytes, and neutrophils). miR-223-3p has been significantly expressed in an acute stage of mastitis (p < 0.01) but not in the chronic or susceptible stages. Conversely, mir-26-5p has been significantly reduced in acute, chronic, and susceptible groups of animals. In immune-cell cultures, miR-26 has been shown to be down-regulated in lipopolysaccharide (LPS)-stimulated neutrophils, while miR-223 has been shown to be up-regulated in phytohemagglutinin (PHA)-stimulated lymphocytes. The differential expression of miR-223-3p and miR-26-5p, combined with differential and total somatic cell count, could serve as a useful tool for identifying the evolutionary stage of mastitis-related inflammatory pathology. Full article
(This article belongs to the Special Issue The Role of Non-Coding RNAs in Health and Disease)
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16 pages, 3195 KiB  
Article
Transcriptomic-Based Identification of miR-125a Novel Targets in Human Hepatocarcinoma Cells
by Ilenia De Leo, Nicola Mosca, Mariaceleste Pezzullo, Danila Valletta, Francesco Manfrevola, Vincenza Grazia Mele, Rosanna Chianese, Aniello Russo and Nicoletta Potenza
Biomolecules 2025, 15(1), 144; https://doi.org/10.3390/biom15010144 - 18 Jan 2025
Viewed by 989
Abstract
Hepatocellular carcinoma (HCC) is among the most aggressive and lethal human tumors. Many functional studies have demonstrated the role of non-coding RNAs (ncRNA), particularly microRNAs (miRNA), in the regulation of hepatocarcinogenesis driving pathways. MiR-125a-5p (miR-125a) has been consistently reported as an oncosuppressive miRNA, [...] Read more.
Hepatocellular carcinoma (HCC) is among the most aggressive and lethal human tumors. Many functional studies have demonstrated the role of non-coding RNAs (ncRNA), particularly microRNAs (miRNA), in the regulation of hepatocarcinogenesis driving pathways. MiR-125a-5p (miR-125a) has been consistently reported as an oncosuppressive miRNA, as demonstrated in vivo and in vitro. However, its HCC relevant targets and molecular mechanisms are still largely unknown. Here, a genome-wide perspective of the whole miR-125a targetome has been achieved. In particular, two different HCC cell lines were subjected to a miRNA boosting by mimic transfections, and consequently many genes were de-regulated, as observed by a transcriptomic approach. The merging of down-regulated genes with results from bioinformatic predictive tools yielded a number of candidate direct targets that were further experimentally validated by luciferase-based reporter assays. Different novel targets were found, in particular ARID3A, CCNJ, LIPA, NR6A1, and NUP210, oncogenes in various tumors and here also related to HCC through miR-125a regulation. The RNA interactions investigated in this work could pave the way to piece together the RNA regulatory networks governed by the miRNA impacting on hepatocarcinogenesis, and be exploited in the future for identifying novel biomarkers and therapeutic targets in HCC. Full article
(This article belongs to the Special Issue The Role of Non-Coding RNAs in Health and Disease)
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Review

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26 pages, 712 KiB  
Review
Unveiling Pharmacogenomics Insights into Circular RNAs: Toward Precision Medicine in Cancer Therapy
by Saud Alqahtani, Taha Alqahtani, Krishnaraju Venkatesan, Durgaramani Sivadasan, Rehab Ahmed, Hassabelrasoul Elfadil, Premalatha Paulsamy and Kalaiselvi Periannan
Biomolecules 2025, 15(4), 535; https://doi.org/10.3390/biom15040535 - 5 Apr 2025
Viewed by 532
Abstract
Pharmacogenomics is revolutionizing precision medicine by enabling tailored therapeutic strategies based on an individual genetic and molecular profile. Circular RNAs (circRNAs), a distinct subclass of endogenous non-coding RNAs, have recently emerged as key regulators of drug resistance, tumor progression, and therapeutic responses. Their [...] Read more.
Pharmacogenomics is revolutionizing precision medicine by enabling tailored therapeutic strategies based on an individual genetic and molecular profile. Circular RNAs (circRNAs), a distinct subclass of endogenous non-coding RNAs, have recently emerged as key regulators of drug resistance, tumor progression, and therapeutic responses. Their covalently closed circular structure provides exceptional stability and resistance to exonuclease degradation, positioning them as reliable biomarkers and novel therapeutic targets in cancer management. This review provides a comprehensive analysis of the interplay between circRNAs and pharmacogenomics, focusing on their role in modulating drug metabolism, therapeutic efficacy, and toxicity profiles. We examine how circRNA-mediated regulatory networks influence chemotherapy resistance, alter targeted therapy responses, and impact immunotherapy outcomes. Additionally, we discuss emerging experimental tools and bioinformatics techniques for studying circRNAs, including multi-omics integration, machine learning-driven biomarker discovery, and high-throughput sequencing technologies. Beyond their diagnostic potential, circRNAs are being actively explored as therapeutic agents and drug delivery vehicles. Recent advancements in circRNA-based vaccines, engineered CAR-T cells, and synthetic circRNA therapeutics highlight their transformative potential in oncology. Furthermore, we address the challenges of standardization, reproducibility, and clinical translation, emphasizing the need for rigorous biomarker validation and regulatory frameworks to facilitate their integration into clinical practice. By incorporating circRNA profiling into pharmacogenomic strategies, this review underscores a paradigm shift toward highly personalized cancer therapies. circRNAs hold immense potential to overcome drug resistance, enhance treatment efficacy, and optimize patient outcomes, marking a significant advancement in precision oncology. Full article
(This article belongs to the Special Issue The Role of Non-Coding RNAs in Health and Disease)
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23 pages, 1691 KiB  
Review
The Role of Long Non-Coding RNAs in Modulating the Immune Microenvironment of Triple-Negative Breast Cancer: Mechanistic Insights and Therapeutic Potential
by Yongcheng Su, Qingquan Bai, Wenqing Zhang, Beibei Xu and Tianhui Hu
Biomolecules 2025, 15(3), 454; https://doi.org/10.3390/biom15030454 - 20 Mar 2025
Viewed by 600
Abstract
Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive subtype of breast cancer that faces therapeutic challenges due to a shortage of effective targeted therapies. The complex biology of TNBC renders its clinical management fraught with difficulties, especially regarding the immune microenvironment [...] Read more.
Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive subtype of breast cancer that faces therapeutic challenges due to a shortage of effective targeted therapies. The complex biology of TNBC renders its clinical management fraught with difficulties, especially regarding the immune microenvironment of the tumor. In recent years, long non-coding RNAs (lncRNAs) have been recognized as important gene regulators with key roles in tumor development and microenvironmental regulation. Previous studies have shown that lncRNAs play important roles in the immune microenvironment of TNBC, including the regulation of tumor immune escape and the function of tumor-infiltrating immune cells. However, despite the increasing research on lncRNAs, there are still many unanswered questions, such as their specific mechanism of action and how to effectively utilize them as therapeutic targets. Therefore, the aim of this study was to review the mechanisms of lncRNAs in the TNBC immune microenvironment, explore their regulatory roles in tumor immune escape and immune cell infiltration, and explore their prospects as potential therapeutic targets. By integrating the latest research results, this study aims to provide new ideas and directions for future TNBC treatment. Full article
(This article belongs to the Special Issue The Role of Non-Coding RNAs in Health and Disease)
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