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RNA in Human Diseases: Challenges and Opportunities: 2nd Edition
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RNA in Human Diseases: Challenges and Opportunities: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 2894

Special Issue Editor

Prof. Dr. Nicoletta Potenza

E-Mail Website
Guest Editor
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania “L. Vanvitelli”, Via Vivaldi, 43-81100 Caserta, Italy
Interests: microRNAs; lncRNA; non-coding RNA; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second volume of our previous Special Issue “RNA in Human Diseases: Challenges and Opportunities”. Our understanding of RNA biology has expanded tremendously over the last two decades. On the one hand, the deep knowledge of post-transcriptional processes sustained by RNA molecules, including splicing, editing, chemical modification, translation and degradation, has revealed the impact of their mis-regulation on human diseases, recently referred to as “RNA disease”. On the other hand, the discovery of a plethora of non-coding RNA biotypes, representing the majority of mammalian transcriptomes, including microRNAs, long non-coding RNAs and circular RNAs, unveiled the previously unappreciated regulatory role of RNA, beyond serving as a carrier of genetic information between DNA and proteins. Many studies revealed functional interactions among coding and non-coding RNAs, often in a competitive way when they bind to shared microRNAs, giving rise to complex RNA regulatory networks, wherein the unbalancing of any network component can act as a driving force for human diseases, as demonstrated for various cancer types.

The double face of RNA biology studies, representing a challenge for human diseases but also an opportunity for therapeutics, has become particularly clear during the COVID-19 pandemic: people outside the research world are also now aware that RNA molecules, even carried by viruses, impact our health but can indeed save the day by exploiting them as innovative and effective vaccines.

This Special Issue welcomes original research manuscripts unraveling new facets of RNA biology and novel RNA regulatory networks, potentially useful as RNA-targeted and RNA-based therapies for drug hunters, or reporting innovative methodological approaches, including new diagnostic and bioinformatic tools, shaping the future of personalized medicine. Critical review manuscripts with an RNA-centric perspective vision setting the stage for future research are also especially welcome.

Prof. Dr. Nicoletta Potenza
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 250 words) can be sent to the Editorial Office for assessment.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • microRNA
  • piRNA
  • lncRNA
  • circRNA
  • RNA therapeutics
  • ceRNET
  • RNA disease
  • RNA processing
  • RNA modification

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Published Papers (4 papers)

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Research

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17 pages, 3246 KB  
Article
Transcriptomic Profiling Reveals Isoform-Specific Regulatory Roles of miR-196A and miR-196B in Colorectal Cancer Cells
by Ji Su Mo, Dong Seok Shin and Youn Ho Han
Int. J. Mol. Sci. 2026, 27(9), 3959; https://doi.org/10.3390/ijms27093959 - 29 Apr 2026
Viewed by 235
Abstract
MicroRNAs (miRNAs) play important roles in the regulation of gene expression and are frequently dysregulated in cancer. Among them, the miR-196 family has been implicated in multiple malignancies, including colorectal cancer (CRC), but the isoform-specific transcriptional effects of miR-196A and miR-196B remain poorly [...] Read more.
MicroRNAs (miRNAs) play important roles in the regulation of gene expression and are frequently dysregulated in cancer. Among them, the miR-196 family has been implicated in multiple malignancies, including colorectal cancer (CRC), but the isoform-specific transcriptional effects of miR-196A and miR-196B remain poorly understood. In this study, we generated miR-196A and miR-196B knockout SW48 CRC cell lines using CRISPR-based genome editing and performed RNA sequencing to investigate the transcriptional consequences of individual miR-196 isoform deletion. Transcriptomic analysis revealed widespread gene expression changes in both knockout models and demonstrated distinct clustering patterns between parental SW48 cells and miR-196-deficient cells. Functional enrichment analysis indicated that the altered genes were associated with biological processes related to cytoskeletal organization, intracellular transport, protein folding, and metabolic regulation. Notably, both shared and isoform-specific transcriptional alterations were observed, suggesting that miR-196A and miR-196B contribute to partially overlapping but distinct regulatory networks in CRC cells. Collectively, these findings provide a comprehensive transcriptomic overview of miR-196 isoform deletion in colorectal cancer cells and highlight potential isoform-dependent transcriptional programs that may contribute to CRC biology. Full article
(This article belongs to the Special Issue RNA in Human Diseases: Challenges and Opportunities: 2nd Edition)
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14 pages, 951 KB  
Article
Analysis of Circulating MicroRNAs in Patients with Diabetic Foot Ulcers and Lower Limb Amputation
by Ricardo Gamboa, Reyna Sámano, Mario Peña-Peña, Vicente Castrejon-Téllez, Alexa Paola Chávez-Nava, Guadalupe Aguilar-Martínez and Claudia Huesca-Gómez
Int. J. Mol. Sci. 2026, 27(8), 3516; https://doi.org/10.3390/ijms27083516 - 14 Apr 2026
Viewed by 751
Abstract
Non-healing diabetic foot ulcers substantially increase the risk of infection and lower limb amputation, contributing to elevated morbidity and mortality among individuals with diabetes. MicroRNAs (miRNAs) have been widely studied as potential early biomarkers for various diseases. This pilot study assessed circulating miRNA [...] Read more.
Non-healing diabetic foot ulcers substantially increase the risk of infection and lower limb amputation, contributing to elevated morbidity and mortality among individuals with diabetes. MicroRNAs (miRNAs) have been widely studied as potential early biomarkers for various diseases. This pilot study assessed circulating miRNA expression profiles in adults with diabetic ulcers (n = 31), individuals who underwent limb amputation due to foot ulcers (n = 20), and 50 control subjects using RT-qPCR. Patients with diabetic foot ulcers and amputations exhibited significantly higher plasma levels of miR-7e, miR-17, miR-33, and miR-191 compared to controls (p < 0.05). Notably, miR-191 expression was significantly greater in patients with limb amputations than in those with diabetic ulcers (p = 0.001). A strong positive correlation was identified between miR-191 and glucose levels (r = 0.682, p = 0.001), while an inverse correlation was observed with HDL-C (r = −0.476, p = 0.034). Let-7e also correlated positively with glucose (r = 0.543, p = 0.013) and negatively with HDL-C (r = −0.491, p = 0.028). Significant associations were found between miR-17-5p and both cholesterol (r = 0.584, p = 0.007) and LDL-C (r = 0.495, p = 0.026). ROC analyses supported the diagnostic value of these miRNAs: miR-17 and miR-191 achieved AUCs of 0.742 (p = 0.000) and 0.671 (p = 0.006), respectively, indicating their potential as biomarkers for disease identification. These findings suggest that increased expression of let-7e, miR-17, and miR-191 may serve as significant biomarkers. Full article
(This article belongs to the Special Issue RNA in Human Diseases: Challenges and Opportunities: 2nd Edition)
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29 pages, 2358 KB  
Article
Subtype-Consistent Upregulation of Ferroptosis-Associated Pathways in Breast Cancer with Heterogeneous Prognostic Implications and Systemic Response to Cryoablation
by Kacper Boroń, Agata Panfil, Tomasz Sirek, Agata Sirek, Nikola Zmarzły, Michalina Wróbel, Zbigniew Wróbel, Dariusz Boron, Piotr Ossowski, Martyna Stefaniak, Paweł Ordon, Grzegorz Wyrobiec, Piotr Wyrobiec, Wojciech Kulej, Natalia Lekston and Beniamin Oskar Grabarek
Int. J. Mol. Sci. 2026, 27(8), 3446; https://doi.org/10.3390/ijms27083446 - 12 Apr 2026
Viewed by 685
Abstract
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress, increasingly implicated in cancer biology. However, its molecular regulation across breast cancer subtypes and its potential systemic manifestations remain incompletely understood. The aim of this study was [...] Read more.
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress, increasingly implicated in cancer biology. However, its molecular regulation across breast cancer subtypes and its potential systemic manifestations remain incompletely understood. The aim of this study was to identify ferroptosis-associated molecular alterations that are largely shared across subtypes and to evaluate their systemic reflection following localized tissue injury. Tumor and matched normal breast tissues representing major molecular subtypes were analyzed. Global mRNA and miRNA expression profiling was performed using microarrays, followed by validation of selected genes using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Functional enrichment and protein–protein interaction analyses were conducted to characterize associated pathways. In addition, systemic responses were assessed in patients undergoing fibroadenoma cryoablation through longitudinal blood sampling. Six ferroptosis-related genes (SLC7A11, GPX4, FTH1, NQO1, NFE2L2, SQSTM1) demonstrated consistent upregulation across all breast cancer subtypes, with higher expression observed in more aggressive tumors. These genes are functionally linked to antioxidant defense, iron metabolism, and oxidative stress regulation, and their coordinated expression pattern is consistent with activation of NRF2-dependent cytoprotective pathways. Downregulation of selected miRNAs may contribute to this expression profile but likely represents a secondary regulatory mechanism. Survival analysis revealed heterogeneous and subtype-dependent associations, with limited and gene-specific prognostic relevance. Cryoablation induced transient increases in circulating levels of the analyzed proteins, reflecting systemic responses to localized tissue injury. In conclusion, breast cancer is characterized by a largely shared ferroptosis-associated molecular signature across subtypes; however, its clinical impact appears to be variable and context-dependent. Systemic detection of related molecular signals suggests potential utility as indicators of tissue stress responses, although their role as specific biomarkers of ferroptosis requires further validation. Full article
(This article belongs to the Special Issue RNA in Human Diseases: Challenges and Opportunities: 2nd Edition)
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Review

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35 pages, 2183 KB  
Review
MicroRNAs in Cardiovascular Diseases: Molecular Networks of Cellular Homeostasis, Inflammation, and Pathological Remodeling
by Humberto Vélez-Slimani and Luis A. Salazar
Int. J. Mol. Sci. 2026, 27(8), 3582; https://doi.org/10.3390/ijms27083582 - 17 Apr 2026
Viewed by 527
Abstract
Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, underscoring the need to better define the molecular mechanisms that govern cardiovascular homeostasis and disease progression. Among post-transcriptional regulators, microRNAs have emerged as important modulators of endothelial function, vascular smooth muscle cell [...] Read more.
Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, underscoring the need to better define the molecular mechanisms that govern cardiovascular homeostasis and disease progression. Among post-transcriptional regulators, microRNAs have emerged as important modulators of endothelial function, vascular smooth muscle cell plasticity, cardiomyocyte integrity, and cardiac fibroblast activity. This narrative review examines how microRNAs orchestrate molecular networks linking cellular homeostasis to inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, fibrosis, angiogenesis, and pathological remodeling across major cardiovascular cell types. It further discusses how these regulatory programs are reflected in specific cardiovascular diseases, including atherosclerosis, hypertension, acute myocardial infarction, heart failure, and arrhythmias. In addition, the review addresses the growing relevance of circulating and extracellular vesicle-associated microRNAs as candidate biomarkers for diagnosis, prognosis, and disease monitoring, as well as their therapeutic potential through mimics, inhibitors, antagomirs, and emerging delivery systems. Finally, current translation barriers are considered, including methodological heterogeneity, limited tissue specificity, delivery challenges, safety concerns, and the need for large-scale clinical validation. Overall, microRNAs are presented as integrative regulators connecting cardiovascular cell biology with disease mechanisms and clinical applications. Full article
(This article belongs to the Special Issue RNA in Human Diseases: Challenges and Opportunities: 2nd Edition)
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