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Putative Epigenetic Regulator microRNAs (epi-miRNAs) and Their Predicted Targets in High-Fat Diet-Induced Cardiac Dysfunction: An In Silico Analysis in Obese Rats

Pipicz, Márton and Biró, Gergő Zalán and Szabó, Márton Richárd and Zvara, Ágnes and Csont, Tamás Bálint (2025) Putative Epigenetic Regulator microRNAs (epi-miRNAs) and Their Predicted Targets in High-Fat Diet-Induced Cardiac Dysfunction: An In Silico Analysis in Obese Rats. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 26 (5). No. 2247. ISSN 1661-6596

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Abstract

Obesity-related cardiac dysfunction is a significant global health challenge. High-fat diets (HFDs) are well-established models of obesity. HFD has been reported to induce cardiac dysfunction and alter cardiac miRNA expression, DNA methylation and histone modifications. Nevertheless, it remains unclear whether cardiac miRNAs altered due to HFD target epigenetic regulator enzymes and function as epigenetic regulator miRNAs (epi-miRNAs), thereby contributing to HFD-induced epigenetic changes and cardiac dysfunction. To address this gap in our knowledge, this study aimed to identify putative cardiac epi-miRNAs and their potential epigenetic targets through an in silico analysis of a previously published miRNA dataset from Sprague Dawley rats subjected to HFD. Using two independent databases, miRDB and miRWalk, predicted miRNA-mRNA interactions were analyzed. A total of 71 miRNAs were identified in our present study as putative epi-miRNAs. A total of 34 epi-miRNAs were upregulated (e.g., miR-92b-3p, let-7c-5p, miR-132-3p), and 37 were downregulated (e.g., miR-21-3p, miR-29c-3p, miR-199a-3p) in response to HFD. Epi-miRNAs targeted 81 individual epigenetic regulators (e.g., Dnmt3a, Ezh2, Hdac4, Kdm3a) with 202 possible miRNA–target interactions. Most of the targeted epigenetic regulators were involved in histone modification. An epi-miRNA–target analysis indicated increased DNA methylation and histone acetylation and decreased histone methylation in the hearts of HFD-fed rats. These findings suggest the importance of epi-miRNA-induced epigenetic changes in HFD-related cardiac dysfunction.

Item Type: Article
Additional Information: This research was also funded by 2023-1.1.1-PIACI_FÓKUSZ-2024-00036, 2020-1.1.6-JÖVŐ-2021-00003 and 2022-1.2.6-TÉT-IPARI-TR-2022-00023 grants from the National Research, Development and Innovation Office (NKFI), Hungary.
Uncontrolled Keywords: high-fat diet; epi-miRNAs; network analysis; cardiac dysfunction; epigenetic regulators; miRNA-mRNA interactions; histone modification; DNA methylation; cardiac remodeling
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 17 Mar 2026 15:38
Last Modified: 17 Mar 2026 15:38
URI: https://real.mtak.hu/id/eprint/235769

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