m⁶A modification-mediated circHOMER1 regulates muscle development and fiber-type transition via the miR-935/MYOZ2 axis.

Authors

Shaojie Qian, Meng Li, Zumei Ming, Yuxuan Gong, Mingxin Wen, Yuqi Han, Xiaohong Guo, Bugao Li

Published in

Cellular signalling. Pages 112996. Nov 09, 2026. Epub Nov 09, 2026.

Abstract

Skeletal muscle development and fiber-type transition are critical determinants of muscle function, metabolic homeostasis, and adaptability to exercise. Dysregulation of these processes is closely linked to various muscle-related diseases. Circular RNAs (circRNAs) and N6-methyladenosine (m⁶A) methylation play important roles in muscle biology; however, their specific contributions to fiber-type transition remain poorly understood. In this study, we investigated the functional role and underlying mechanism of circHOMER1, a porcine skeletal muscle-associated circRNA identified in our previous screening, in regulating muscle fiber-type transformation. Functional assays conducted both in vitro and in vivo demonstrated that circHOMER1 significantly promotes myogenic differentiation and induces glycolytic (type IIb) fiber formation. At the upstream regulatory level, FTO knockdown increased the m⁶A modification level and stability of circHOMER1 while reducing its interaction with the m⁶A reader YTHDC2. Additionally, YTHDC2 knockdown prolonged circHOMER1 stability. These findings suggest that FTO and YTHDC2 are involved in the m⁶A-associated regulation of circHOMER1 stability, which may contribute to muscle fiber-type transition. Further mechanistic studies revealed that circHOMER1 acts as a competing endogenous RNA (ceRNA), sponging miR-935 and thereby relieving its inhibitory effect on MYOZ2, a key regulator of muscle differentiation and glycolytic fiber generation. In summary, this study provides insights into the role of m⁶A-associated regulation in circHOMER1 stability and the involvement of the circHOMER1/miR-935/MYOZ2 axis in porcine muscle development and fiber-type transition. These findings offer novel epigenetic insights into the regulation of muscle phenotype and potential therapeutic targets for muscle-related diseases.

PMID:
43003165
Bibliographic data and abstract were imported from PubMed on 10 Nov 2026.

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