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环状RNA circAtxn10通过靶向miR-143-3p和Chrna1调控骨骼肌细胞分化。

Circular RNA circAtxn10 regulates skeletal muscle cell differentiation by targeting miR-143-3p and Chrna1.

作者信息

Choe Nakwon, Jeong Anna, Joung Hosouk, Jeong Dongtak, Kim Young-Kook, Kook Hyun, Kwon Duk-Hwa

机构信息

Department of Pharmacology, Chonnam National University Medical School, Hwasun 58128, Korea.

BK21 plus Center for Creative Biomedical Scientists, Chonnam National University, Gwangju 61186, Korea.

出版信息

Korean J Physiol Pharmacol. 2025 Sep 1;29(5):637-648. doi: 10.4196/kjpp.25.046. Epub 2025 Jul 24.

Abstract

Skeletal muscle differentiation is a complex process regulated by a network of genes and transcription factors. Recent studies have revealed the roles of circular RNAs (circRNAs) and microRNAs (miRNAs) in modulating gene expression during myogenesis. In this study, we focused on the functional interplay between circAtxn10, miR-143-3p, and the nicotinic acetylcholine receptor subunit alpha 1 (Chrna1) in skeletal muscle differentiation. Our results demonstrate that circAtxn10 expression increases during myogenic differentiation and acts as a sponge for miR-143-3p through direct binding. We identified Chrna1 as a direct target of miR-143-3p through three binding sites in its 3'-UTR and showed that both miR-143-3p mimic and Chrna1 knockdown significantly impair myogenesis. Notably, Chrna1 overexpression dramatically enhanced myogenic marker expression and myotube formation. Our findings establish a regulatory axis involving circAtxn10, miR-143-3p, and Chrna1 that plays a critical role in modulating skeletal muscle differentiation, providing new insights into the complex molecular mechanisms regulating myogenesis.

摘要

骨骼肌分化是一个由基因和转录因子网络调控的复杂过程。最近的研究揭示了环状RNA(circRNA)和微小RNA(miRNA)在肌生成过程中调节基因表达的作用。在本研究中,我们聚焦于circAtxn10、miR-143-3p和烟碱型乙酰胆碱受体α1亚基(Chrna1)在骨骼肌分化中的功能相互作用。我们的结果表明,circAtxn10在肌源性分化过程中表达增加,并通过直接结合作为miR-143-3p的海绵。我们通过Chrna1 3'-UTR中的三个结合位点确定其为miR-143-3p的直接靶点,并表明miR-143-3p模拟物和Chrna1敲低均显著损害肌生成。值得注意的是,Chrna1过表达显著增强了肌源性标志物的表达和肌管形成。我们的研究结果建立了一个涉及circAtxn10、miR-143-3p和Chrna1的调控轴,该调控轴在调节骨骼肌分化中起关键作用,为调控肌生成的复杂分子机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b3d/12381802/3398fa0eba8c/kjpp-29-5-637-f1.jpg

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