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Biomedicines
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MicroRNA and Its Role in Human Health, 2nd Edition
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MicroRNA and Its Role in Human Health, 2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 October 2025) | Viewed by 9179

Editor

Dr. Shih-Yao Chen

E-Mail Website
Guest Editor
Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology—Taiwan, Tainan, Taiwan
Interests: rheumatic disease; microRNA expression; microRNA regulation; molecular mechanism; molecular therapy; molecular diagnosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

MicroRNAs (miRs) are fascinating, small, noncoding RNA molecules that play a pivotal role in human health. With an ever-growing body of evidence, miRs have emerged as key players in diagnosing diseases, developing novel therapeutic strategies, and unveiling the intricate molecular mechanisms and signaling pathways that govern various disease processes. miRs function by binding to the 3'-untranslated regions of specific messenger RNAs (mRNAs), leading to their degradation or the suppression of translation. This ability to upregulate or downregulate target genes based on miR expression levels provides a unique window into understanding disease progression and regulation. By exploring miR expression and target gene interactions, we can unlock new avenues for therapeutic interventions.

The regulation of miRs can be harnessed using cutting-edge techniques, including vector-based miR precursors or sponges, agomiR or antagomiR transfer, and genome editing via CRISPR. Additionally, high-throughput miR arrays offer large-scale data that can uncover novel disease associations, expanding our understanding of the roles miRs play in human health.

In this Special Issue, we aim to present a comprehensive collection of studies exploring the diverse roles of miRs across a wide range of disease models. We encourage the submission of original research articles and comprehensive reviews that examine miRs as diagnostic markers, therapeutic agents, or key pathogenic molecules. We are excited to collaborate with you on this cutting-edge exploration of microRNAs and look forward to your valuable contributions to the progression of this dynamic field.

Dr. Shih-Yao Chen
Guest Editor

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Keywords

  • microRNA
  • disease models
  • disease associations
  • molecular mechanism
  • molecular diagnosis
  • molecular therapy

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Published Papers (5 papers)

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22 pages, 1827 KB  
Article
Effect of Osteoblast-Derived Extracellular Vesicles on Osteosarcoma Cells’ Transcriptional Profile: Role of Shuttled miRNAs
by Luca Giacchi, Argia Ucci, Veronica Zelli, Chiara Compagnoni, Elisa Pucci, Alessandra Tessitore, Marco Ponzetti and Nadia Rucci
Biomedicines 2026, 14(5), 1039; https://doi.org/10.3390/biomedicines14051039 - 3 May 2026
Viewed by 943
Abstract
Background/Objectives: Osteosarcoma is the most common primary malignant bone tumour, affecting children and young adults. Recent evidence suggests that extracellular vesicles (EVs), small membrane-bound nanoparticles released by all cell types, play a key role in intercellular communication within the tumour microenvironment. Therefore, [...] Read more.
Background/Objectives: Osteosarcoma is the most common primary malignant bone tumour, affecting children and young adults. Recent evidence suggests that extracellular vesicles (EVs), small membrane-bound nanoparticles released by all cell types, play a key role in intercellular communication within the tumour microenvironment. Therefore, we aimed to investigate the effects of osteoblast-derived EVs (OB-EVs) on osteosarcoma cell behaviour and to characterise the transcriptional and miRNA-mediated mechanisms underlying these effects. Methods: Phenotypic assays were performed to assess metabolic activity, proliferation, apoptosis, and invasion ability of human osteosarcoma cell lines after treatment with OB-EVs. Illumina-based RNAseq was conducted on RNA isolated from OB-EVs-treated cells, and qRT-PCR was assessed using commercially available TaqMan miRNA cards on RNA isolated from OB-EVs. Results: In U2OS cells, OB-EVs reduced metabolic activity (1.30-fold decrease, p = 0.0137) and proliferation (1.70-fold decrease, p = 0.017) while increasing apoptosis (1.15-fold increase, p = 0.014). In MG63, OB-EVs increased proliferation (4.9-fold increase, p = 0.020) without affecting tumour cell aggressiveness, while normal osteoblast behaviour was not affected by OB-EVs. MNNG/HOS cells treated with OB-EVs for 48 h showed substantial transcriptomic changes, with 296 differentially expressed genes (97 up- and 199 down-regulated in OB-EVs treated cells versus untreated cells), indicating a direct impact of OB-EVs on gene expression. Intriguingly, Gene Set Enrichment Analysis (GSEA) showed trends consistent with modulation of signalling pathways, including Wnt/β-catenin and NOTCH. Conversely, miRNA profiling of OB-EVs identified 13 highly expressed miRNA. Integration of transcriptomic and miRNA target prediction data highlighted convergent pathway-level signals, suggesting that OB-EVs may modulate tumour-associated regulatory networks. Conclusions: Taken together, these findings indicate that OB-EVs modulate osteosarcoma cell phenotype, with miRNA shuttling representing a potentially relevant contributing mechanism. The integrative analysis suggests that pathways associated with proliferation and cellular homeostasis, including Wnt/β-catenin signalling, may be involved, although further functional validation is required to confirm these mechanisms. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health, 2nd Edition)
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22 pages, 2583 KB  
Article
Chronic Resistance Exercise Combined with Nutrient Timing Enhances Skeletal Muscle Mass and Strength While Modulating Small Extracellular Vesicle miRNA Profiles
by Dávid Csala, Zoltán Ádám, Zoltán Horváth-Szalai, Balázs Sebesi, Kitti Garai, Krisztián Kvell and Márta Wilhelm
Biomedicines 2026, 14(1), 127; https://doi.org/10.3390/biomedicines14010127 - 8 Jan 2026
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Abstract
Background: The anabolic window hypothesis suggests a limited post-exercise period for optimal nutrient uptake and utilization. Prior research indicates that miRNAs in extracellular vesicles (EVs) may regulate post-exercise adaptation by influencing protein synthesis. This study aimed to examine the effects of resistance [...] Read more.
Background: The anabolic window hypothesis suggests a limited post-exercise period for optimal nutrient uptake and utilization. Prior research indicates that miRNAs in extracellular vesicles (EVs) may regulate post-exercise adaptation by influencing protein synthesis. This study aimed to examine the effects of resistance exercise (RE) on physiological parameters and the expression and function of miRNAs transported in EVs. Methods: Twenty resistance-trained male participants (22 ± 2 years) completed a five-week RE program designed for hypertrophy. They consumed maltodextrin and whey protein based on assigned nutrient timing: immediately post-exercise (AE), three hours post-exercise (AE3), or no intake (CTRL). Body composition and knee extensor strength were assessed. Small EVs were isolated and then validated via three methods. Nanoparticle tracking analysis determined EV concentration and size, followed by pooled miRNA profiling and signaling pathway analysis. Results: Skeletal muscle mass significantly increased in AE (p = 0.001, g = 2) and AE3 (p = 0.028, g = 1), and it was higher in AE compared to CTRL (p = 0.013, η2 = 0.41), while knee extensor strength improved only in AE (p = 0.032, g = 0.9). Body fat percentage significantly decreased in all groups, AE (p = 0.005, g = 1.5), AE3 (p = 0.024, g = 1), and CTRL (p = 0.005, g = 1.7). Vesicle concentration significantly increased in the AE group (p = 0.043, r = 0.7), while it decreased in the CTRL group (p = 0.046, r = 0.8). Distinct miRNA expression profiles emerged post-intervention: 20 miRNAs were upregulated in AE, while 13 in AE3 and 15 in CTRL were downregulated. Conclusions: Nutrient timing influences training adaptation but is not more critical than total macronutrient intake. Changes in EV-transported miRNAs may regulate anabolic processes via the PI3K-AKT-mTOR and FoxO pathways through PTEN regulation. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health, 2nd Edition)
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24 pages, 6945 KB  
Article
Circular Nucleic Acids Act as an Oncogenic MicroRNA Sponge to Inhibit Hepatocellular Carcinoma Progression
by Qianyi Zhang, Pengcheng Sun, Guang Hu, Xuanyao Yu, Wen Zhang, Xuan Feng, Lan Yu and Pengfei Zhang
Biomedicines 2025, 13(5), 1171; https://doi.org/10.3390/biomedicines13051171 - 11 May 2025
Cited by 7 | Viewed by 2558 | Correction
Abstract
Background: Aberrant expression of microRNAs in neoplastic lesions may serve as potential personalized therapeutic targets. To inhibit oncogenic microRNAs (oncomiRs) expression and restore tumor suppressor proteins, linear miRNA sponges have been developed, leading to several drugs in clinical trials. Despite their efficacy, chemically [...] Read more.
Background: Aberrant expression of microRNAs in neoplastic lesions may serve as potential personalized therapeutic targets. To inhibit oncogenic microRNAs (oncomiRs) expression and restore tumor suppressor proteins, linear miRNA sponges have been developed, leading to several drugs in clinical trials. Despite their efficacy, chemically synthesized miRNA inhibitors face challenges with sustained inhibition and high production costs, hindering widespread clinical adoption. Additionally, single-stranded circular RNAs (circRNAs) act as miRNA sponges, enhancing protein expression and demonstrating stability and therapeutic potential in cancer treatment. Our approach involves the use of synthetic single-stranded circular nucleic acids, including circDNA and circRNA, to selectively target and inhibit a variety of aberrantly overexpressed oncomiRs in tumors. The objective of this strategy is to restore the expression levels of multiple tumor suppressor factors and to suppress the malignant progression of tumors. Methods: Our methodology comprises a two-step process. First, we identified tumor suppressor genes (TSGs) with abnormally low expression in hepatocellular carcinoma (HCC) tumor cells by transcriptomic analysis and targeted the upstream cancer miRNA clusters of these TSGs. Second, we designed and validated a fully complementary circDNA or circRNA construct, ligated by T4 DNA ligase or T4 RNA ligase, respectively, that specifically targets the sponge oncomiRs both in vitro and in vivo to inhibit the malignant progression of HCC. Results: CircNAs demonstrated superior, long-lasting therapeutic efficacy against HCC compared to inhibitors. Furthermore, we compared the immune effects in vivo of three different nucleic acid adsorption carriers, including commercial miRNA inhibitor, circDNA, and circRNA. We found that the miRNA inhibitor activates a more robust inflammatory response compared to circDNA and circRNA. Conclusions: These findings underscore the substantial therapeutic potential of circDNA in tumorigenesis and provide novel insights for the formulation of personalized treatment plans for malignant tumors, such as HCC. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health, 2nd Edition)
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18 pages, 3855 KB  
Article
Differential Pattern of Circulating MicroRNA Expression in Patients with Intracranial Atherosclerosis
by Marine M. Tanashyan, Anton A. Raskurazhev, Alla A. Shabalina, Andrey S. Mazur, Vladislav A. Annushkin, Polina I. Kuznetsova, Sergey N. Illarioshkin and Mikhail A. Piradov
Biomedicines 2025, 13(2), 514; https://doi.org/10.3390/biomedicines13020514 - 19 Feb 2025
Cited by 4 | Viewed by 1588
Abstract
Background: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet fundamental studies regarding epigenetic regulation of ICAS are lacking. We hypothesized that, due to anatomical and/or functional differences, extracranial atherosclerosis is distinct from ICAS, which may explain the clinical variability as [...] Read more.
Background: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet fundamental studies regarding epigenetic regulation of ICAS are lacking. We hypothesized that, due to anatomical and/or functional differences, extracranial atherosclerosis is distinct from ICAS, which may explain the clinical variability as well. Methods: We chose a number of miRNAs involved in various steps of atherogenesis (namely, miR-712/205-5p/-3p, miR-106b-3p/-5p, miR-146a-3p/-5p, miR-100-3p/miR-5p, miR-200c-3p/-5p, miR-532-3p/-5p, and miR-126-3p/-5p) and examined their plasma levels in a cohort of patients with carotid stenosis > 50% (n = 35, mean age: 65 years, 54% male; 12 patients had ICAS). Results: A differential pattern of circulating miR expression was found in ICAS patients: there was an overexpression of miR-712/205-5p, miR-106b-5p, miR-146a-5p, miR-200c-5p, miR-532-3p, and miR-126-3p. The following miRs were underexpressed in intracranial atherosclerosis—miR-712/205-3p and miR-100-3p. These changes represent a plethora of atherogenic mechanisms: smooth muscle cell migration (miR-712/205, miR-532), foam cell formation (miR-106b, miR-146a), endothelial dysfunction (miR-200c), low-density lipoprotein-induced vascular damage (miR-100), and leukocyte recruitment (miR-126). In symptomatic ICAS patients, we observed a statistically significant upregulation of miR-712/205-3p and miR-146a-5p. Conclusions: Overall, the findings of our pilot study revealed several new and interesting associations: (1) intracranial atherosclerosis seems to have a different epigenetic profile (regarding circulating microRNA expression) than isolated extracranial vessel involvement; (2) ischemic stroke in ICAS may be potentiated by other pathophysiologic mechanisms than in extracranial-only atherosclerosis (ECAS). Certain miRs (e.g., miR-712/205) seem to have a larger impact on ICAS than on extracranial atherosclerosis; this may be potentially linked to difference between extra- and intracranial artery morphology and physiology, and/or may lead to the said differences. This underscores the importance of making a distinction in future epigenetic studies between ECAS and ICAS, as the mechanisms of atherogenesis are likely to vary. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health, 2nd Edition)
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2 pages, 138 KB  
Correction
Correction: Zhang et al. Circular Nucleic Acids Act as an Oncogenic MicroRNA Sponge to Inhibit Hepatocellular Carcinoma Progression. Biomedicines 2025, 13, 1171
by Qianyi Zhang, Pengcheng Sun, Guang Hu, Xuanyao Yu, Wen Zhang, Xuan Feng, Lan Yu and Pengfei Zhang
Biomedicines 2025, 13(10), 2394; https://doi.org/10.3390/biomedicines13102394 - 29 Sep 2025
Viewed by 626
Abstract
There was an error in the original publication [...] Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health, 2nd Edition)
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