ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Epigenomics and Epigenetics

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1600103

This article is part of the Research TopicChromatin Modifications and Gene Expression: From Mechanisms to Therapeutic Implications in DiseaseView all articles

MiR-425-5p intervenes in autoimmune myocarditis by regulating Treg cell differentiation through NRAS

Provisionally accepted
Shan  ZhouShan Zhou1Li  ZhangLi Zhang1xiuyun  duanxiuyun duan1keyu  Liukeyu Liu1You  YingnanYou Yingnan1mengjie  mamengjie ma1Bo  HanBo Han2*
  • 1Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong first Medical University, Jinan, Shandong Province, China
  • 2Shandong Provincial Hospital, Jinan, China

The final, formatted version of the article will be published soon.

Aim: Our Previous research revealed significant differences in exosome-mediated intercellular miR-425a-5p between normal children and those with fulminant myocarditis. We sought to elucidate the molecular underpinnings and functional implications of miR-425a-5p in the context of myocarditis progression.Methods: Bioinformatics techniques were employed to predict NRAS as the target gene of miR-425a-5p. We constructed a cellular myocarditis paradigm through LPSmediated provocation of AC16 cardiomyocyte cultures. MiR-425a-5p was overexpressed, and the expressions of NRAS, cell apoptosis, and proinflammatory cytokine profiles, encompassing IL-1β, IL-6, and TNF-α, were comprehensively quantified. An experimental autoimmune myocarditis (EAM) mouse model was created using adeno-associated virus (AAV) for miR-425a-5p overexpression. Comprehensive histopathological analyses were conducted utilizing multiple staining techniques, including hematoxylin-eosin (HE), immunohistochemical, and Masson trichrome methodologies to characterize tissue responses. Results: The study demonstrated that miR-425a-5p alleviated the inflammatory response in both AC16 cells and EAM mice through NRAS mediation. Single-cell data analysis of cardiac immune cells revealed that miR-425a-5p promoted Treg cell differentiation and improved cardiac function. Conclusion: MiR-425a-5p plays a crucial role in modulating inflammatory responses in myocarditis, potentially offering a novel therapeutic strategy for managing the disease.

Keywords: miR-425-5p, Myocarditis, Treg, NRAS, Immunity

Received: 25 Mar 2025; Accepted: 30 Apr 2025.

Copyright: © 2025 Zhou, Zhang, duan, Liu, Yingnan, ma and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Bo Han, Shandong Provincial Hospital, Jinan, China

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