circINSR Promotes Proliferation and Reduces Apoptosis of Embryonic Myoblasts by Sponging miR-34a

Mol Ther Nucleic Acids. 2020 Mar 6:19:986-999. doi: 10.1016/j.omtn.2019.12.032. Epub 2020 Jan 14.

Abstract

As a diverse and abundant class of endogenous RNAs, circular RNAs (circRNAs) participate in processes including cell proliferation and apoptosis. Nevertheless, few researchers have investigated the function of circRNAs in bovine muscle development. Based on existing sequencing data, we identified circINSR. The localization of circINSR in bovine myoblasts was investigated by fluorescence in situ hybridization. Molecular and biochemical assays were used to confirm the role of circINSR in myoblast proliferation and the cell cycle. Mitochondrial membrane potential and annexin V-PE/7-AAD staining assays were performed to assess cell apoptosis. Additionally, interactions between circINSR, miR-34a, and target mRNAs were examined using bioinformatics, a luciferase assay, and RNA immunoprecipitation. We found that circINSR was highly expressed in embryonic muscle tissue. Overexpression of circINSR significantly promoted proliferation and reduced apoptosis of embryonic myoblasts. Our data suggested that circINSR may act as a sponge of miR-34a and could function through de-repression of target genes in muscle cells. This study proposes that circINSR may function as a regulator of embryonic muscle development. circINSR regulates cells proliferation and apoptosis through miR-34a-modulated Bcl-2 and CyclinE2 expression.

Keywords: bovine; circular RNAs; miR-34a; muscle development; proliferation.