LncRNA TUG1 acts as a competing endogenous RNA to mediate CTGF expression by sponging miR‐133b in myocardial fibrosis after myocardial infarction

Abstract

Myocardial fibrosis is one of the basic causes of many cardiovascular diseases. Noncoding RNAs (ncRNAs), including microRNA (miRNA) and long noncoding RNA (lncRNA), have been reported to play an indispensable role in myocardial fibrosis. The current work is focused on investigating the biological role of lncRNA TUG1 in activating cardiac myofibroblasts as well as the underlying mechanism. The outcome revealed that after myocardial infarction TUG1 expression increased and miR-133b expression decreased in the rat model of myocardial fibrosis. The expression level of TUG1 increased following AngII treatment in cardiac myofibroblast. TUG1 knockdown inhibited the Ang-II induced cardiac myofibroblast activation and TUG1 overexpression increased proliferation and collagen generation of cardiac myofibroblasts. Bioinformatic prediction programs predicted that TUG1 had MRE directly combined with miR-133b seed sequence, luciferase activity, and RIP experiments indicated that TUG1, acted as a sponger and interacted with miR-133b in cardiac myofibroblasts. Furthermore, a target of miR-133b was CTGF and CTGF knockdown counteracted the promotion of myocardial fibrosis by miR-133b knockdown. Collectively, our study suggested that TUG1 mediate CTGF expression by sponging miR-133b in the activation of cardiac myofibroblasts. The current work reveals a unique role of the TUG1/miR-133b/CTGF axis in myocardial fibrosis, thus suggesting its immense therapeutic potential in the treatment of cardiac diseases.