Division of Farm Animal Genetic Resources Exploration and Innovation, Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, Public Republic of China, 611130.
Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, Public Republic of China, 710072.
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20191327.
MiR-33a is found as a regulator of cell proliferation in many cancer cells. However, it remains unknown if and how miR-33a plays a role in myoblast proliferation. To investigate the effect of miR-33a on myoblast proliferation, miR-33a mimic or inhibitor was co-administered with or without insulin-like growth factor 1 (IGF1) to simulation myoblasts. Our study showed that up-regulation of miR-33a impaired myoblast proliferation, while down-regulation of miR-33a enhanced myoblast proliferation. Mechanistically, we examined that miR-33a can inhibit the transcription of IGF1, follistatin (FST) and cyclin D1 (CCND1) by targeting their 3'UTR region in both HEK293T cells and duck myoblasts. Moreover, up-regulation of miR-33a decreased and its down-regulation increased the mRNA expression of PI3K, Akt, mTOR and S6K. Importantly, the decreased PI3K, Akt, mTOR and S6K expression by miR-33a mimics was abrogated by co-administered with IGF1. Altogether, our results demonstrated that miR-33a may directly target IGF1, FST and CCND1 to inhibit myoblast proliferation via PI3K/Akt/mTOR signaling pathway. In conclusion, miR-33a is a potential negative regulator of myoblast proliferation and by modulating its expression could promote the early development of skeletal muscle.
miR-33a 在许多癌细胞中被发现是细胞增殖的调节剂。然而，miR-33a 是否以及如何在成肌细胞增殖中发挥作用仍不清楚。为了研究 miR-33a 对成肌细胞增殖的影响，将 miR-33a 模拟物或抑制剂与胰岛素样生长因子 1（IGF1）一起给药或不一起给药来模拟成肌细胞。我们的研究表明，miR-33a 的上调抑制了成肌细胞的增殖，而下调 miR-33a 增强了成肌细胞的增殖。从机制上讲，我们检查了 miR-33a 可以通过靶向其 3'UTR 区域来抑制 HEK293T 细胞和鸭成肌细胞中 IGF1、卵泡抑素（FST）和细胞周期蛋白 D1（CCND1）的转录。此外，miR-33a 的上调减少，而下调则增加了 PI3K、Akt、mTOR 和 S6K 的 mRNA 表达。重要的是，miR-33a 模拟物下调的 PI3K、Akt、mTOR 和 S6K 表达被 IGF1 共给药所消除。总之，我们的结果表明，miR-33a 可能通过 PI3K/Akt/mTOR 信号通路直接靶向 IGF1、FST 和 CCND1 来抑制成肌细胞增殖。总之，miR-33a 是成肌细胞增殖的潜在负调节剂，通过调节其表达可以促进骨骼肌的早期发育。
