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微小RNA-424-5p靶向热休克蛋白90α家族成员1,以促进骨骼肌发育中的增殖并抑制分化。

MiR-424-5p targets HSP90AA1 to facilitate proliferation and restrain differentiation in skeletal muscle development.

作者信息

Chen Xi, Zhu Ying, Song Chengchuang, Chen Yaqi, Wang Yanhong, Lai Min, Zhang Chunlei, Fang Xingtang

机构信息

School of Life Science, Institute of Cellular and Molecular Biology, Jiangsu Normal University, Xuzhou, China.

Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China.

出版信息

Anim Biotechnol. 2023 Dec;34(7):2514-2526. doi: 10.1080/10495398.2022.2102032. Epub 2022 Jul 23.

DOI:10.1080/10495398.2022.2102032
PMID:35875894
Abstract

MiR-424-5p was found to be a potential regulator in the proliferation, migration, and invasion of various cancer cells. However, the effects and functional mechanism of miR-424-5p in the process of myogenesis are still unclear. Previously, using microRNA (miRNA) sequencing and expression analysis, we discovered that miR-424-5p was expressed differentially in the different skeletal muscle growth periods of Xuhuai goats. We hypothesized that miR-424-5p might play an important role in skeletal muscle myogenesis. Then, we found that the proliferation ability of the mouse myoblast cell (C2C12 myoblast cell line) was significantly augmented, whereas the C2C12 differentiation was repressed after increasing the expression of miR-424-5p. Mechanistically, HSP90AA1 presented a close interrelation with miR-424-5p, which was predicted as a target gene in the progression of skeletal muscle myogenesis, using transcriptome sequencing, dual luciferase reporter gene detection, and qRT-PCR. The silencing of HSP90AA1 obviously increased C2C12 proliferation and diminished differentiation, which is consistent with the ability of miR-424-5p in C2C12. Altogether, our findings indicated the role of miR-424-5p as a novel potential regulator via HSP90AA1 during muscle myogenesis progression.

摘要

MiR-424-5p被发现是多种癌细胞增殖、迁移和侵袭的潜在调节因子。然而,miR-424-5p在成肌过程中的作用和功能机制仍不清楚。此前,通过微小RNA(miRNA)测序和表达分析,我们发现miR-424-5p在徐淮山羊不同骨骼肌生长时期存在差异表达。我们推测miR-424-5p可能在骨骼肌成肌过程中发挥重要作用。随后,我们发现增加miR-424-5p的表达后,小鼠成肌细胞(C2C12成肌细胞系)的增殖能力显著增强,而C2C12分化受到抑制。机制上,通过转录组测序、双荧光素酶报告基因检测和qRT-PCR发现,HSP90AA1与miR-424-5p密切相关,HSP90AA1被预测为骨骼肌成肌过程中的一个靶基因。沉默HSP90AA1明显增加C2C12的增殖并减少其分化,这与miR-424-5p对C2C12的作用一致。总之,我们的研究结果表明,在肌肉成肌过程中,miR-424-5p通过HSP90AA1作为一种新的潜在调节因子发挥作用。

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