lncRNA SRA1 Promotes the Activation of Cardiac Myofibroblasts Through Negative Regulation of miR-148b.

Long noncoding RNAs (lncRNAs) have been reported to play a key role in diversity cardiovascular diseases, including cardiac fibrosis. The present study aims to investigate the biological role of lncRNA SRA1 in the activation of cardiac myofibroblasts and the underlying mechanism. Results showed that the expression of SRA1 was upregulated accompanied by cardiac fibrosis in an abdominal aortic banding-treated rat model. Ang-II treatment increased the SRA1 expression of cardiac myofibroblasts, whereas SRA1 knockdown by siRNA inhibited the proliferation, myofibroblast conversion, and collagen production of cardiac myofibroblasts induced by Ang-II. SRA1 overexpression by pcDNA3.1 SRA1-stimulated cardiac myofibroblast activation. To further investigate the underlying mechanism, miR-148b was predicted to be a targeted microRNA of SRA1. Different methods, including sequence alignment, luciferase activity, and MS2 RNA immunoprecipitation were performed to detect the interaction between SRA1 and miR-148b, which suggested that SRA1 negatively regulated miR-148b in cardiac myofibroblasts. Moreover, miR-148b knockdown stimulated cardiac myofibroblast activation, and miR-148b mediated promoting effect of SRA1 on cardiac myofibroblast activation. Collectively, our study suggested that SRA1 promoted cardiac myofibroblast activation by acting as a competitive endogenous RNAs for miR-148b. SRA1 may be a novel potential target for the prevention or therapy of cardiac fibrosis.