MicroRNA-33a negatively regulates myoblast proliferation by targeting IGF1, follistatin and cyclin D1

Abstract

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 myoblasts proliferation. To investigate the effect of miR-33a on myoblasts 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 upregulation of miR-33a impaired myoblasts proliferation, while downregulation of miR-33a enhanced myoblasts 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, upregulation of miR-33a decreased and its downregulation 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 myoblasts proliferation via PI3K/Akt/mTOR signaling. In conclusion, miR-33a is a potential negative regulator of myoblasts proliferation and by modulating its expression. miR-33a could play an important role in promoting the early development of skeletal muscle.