Circular RNA TTN Acts As a miR-432 Sponge to Facilitate Proliferation and Differentiation of Myoblasts via the IGF2/PI3K/AKT Signaling Pathway

Xiaogang Wang; Xiukai Cao; Dong Dong; Xuemei Shen; Jie Cheng; Rui Jiang; Zhaoxin Yang; Shujun Peng; Yongzhen Huang; Xianyong Lan; Ibrahim Elsaeid Elnour; Chuzhao Lei; Hong Chen

doi:10.1016/j.omtn.2019.10.019

Circular RNA TTN Acts As a miR-432 Sponge to Facilitate Proliferation and Differentiation of Myoblasts via the IGF2/PI3K/AKT Signaling Pathway

Mol Ther Nucleic Acids. 2019 Dec 6:18:966-980. doi: 10.1016/j.omtn.2019.10.019. Epub 2019 Oct 25.

Authors

Affiliations

¹ Shaanxi Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Northwest A&F University, Shaanxi 712100, China.
² Shaanxi Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Northwest A&F University, Shaanxi 712100, China. Electronic address: chenhong1212@263.net.

Abstract

Circular RNAs (circRNAs) are ubiquitous endogenous RNA found in various organisms that can regulate gene expression in eukaryotes. However, little is known about potential roles for circRNAs in muscle development. We analyzed circRNA sequencing data of bovine skeletal muscle tissue and found differential expression of circTitin (circTTN) in fetal and adult bovine muscle tissue. We then further studied the role of circTTN in bovine muscle development. Overexpression and inhibition of circTTN together elicited its promoting roles in proliferation and differentiation of bovine primary myoblasts. Mechanistically, circTTN showed interaction with miR-432 by luciferase screening and RNA immunoprecipitation (RIP) assays. Additionally, miR-432 is a regulator of insulin-like growth factor 2 (IGF2), as indicated by luciferase activity, quantitative real-time PCR, and western blotting assays. Increased miR-432 expression inhibited the expression of IGF2, but this effect was remitted by circTTN. Conclusively, our results showed that circTTN promoted proliferation and differentiation of bovine primary myoblasts via competitively combining with miR-432 to activate the IGF2/phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway.

Keywords: IGF2/PI3K/AKT pathway; bovine; circRNA; miRNA; myoblast.