LncRNA MHRT promotes cardiac fibrosis via miR-3185 pathway following myocardial infarction

Abstract

Long-chain noncoding RNA (lncRNA) is a new class of molecular regulators in heart development and disease. However, the role of specific lncRNA in cardiac fibrosis remains to be fully explored. This study aimed to investigate the role and potential mechanism of lncRNA MHRT in myocardial fibrosis after myocardial infarction (MI). Cardiac fibroblasts (CFs) were isolated from a mouse model of MI. The expression levels of MHRT and miR-3185 in the hearts of MI and CFs mice treated with transforming growth factor beta 1 (TGF-β1) were analyzed by qRT-PCR. The collagen expression was assessed using qRT-PCR and Western blot. Cell proliferation was assessed by performing MTT and EdU assays. The direct interaction between lncRNA and miRNA was analyzed by luciferase assay, RNA-binding protein immunoprecipitation (RIP) assay, and RNA pull-down assay. The expression levels of MHRT were raised in MI and CFs mice treated with TGF-β1. Overexpression of MHRT promoted collagen production and CF proliferation, while silencing of MHRT showed the opposite ef-fect. MiR-3185 was a target gene of MHRT. In addition, overexpression of MHRT reduced the expression levels of miR-3185, and siMHRT reversed the inhibitory effect of TGF-β1 on the expression of miR-3185. Overex-pression of miR-3185 inhibited the upregulation of Col I and Col III induced by TGF-β1. MHRT promoted cardiac fibrosis after MI through miR-3185 and increased myocardial collagen deposition and promoted myocardial fibrosis.