miR-142-5p and miR-212-5p cooperatively inhibit the proliferation and collagen formation of cardiac fibroblasts by regulating c-Myc/TP53INP1.

The aim of this study was to investigate the effect and mechanism of miR-142-5p/212-5p on the proliferation and collagen formation of cardiac fibroblasts (CFs) after myocardial infarction (MI). The mouse MI model was established by ligation of the left anterior descending coronary artery. CFs were induced by transforming growth factor-beta 1 (TGF-β1) or angiotensin (Ang II). The molecule expressions were measured by qRT-PCR and Western blot. CF proliferation was detected by an MTT assay. The effect of miR-142-5p/212-5p on the luciferase activity of c-Myc 3'UTR was assessed by the luciferase reporter assay. miR-142-5p and miR-212-5p were downregulated in cardiac tissues of MI mice and in TGF-β1- or Ang II-induced CFs, while the protein levels of collagen I and III were upregulated. Moreover, simultaneous overexpression of miR-142-5p/212-5p inhibited the proliferation and collagen formation of TGF-β1- or Ang II-stimulated CFs to a greater extent than either miR-142-5p or miR-212-5p overexpression alone. MiR-142-5p/212-5p targeted c-Myc and negatively regulated its expression. The effects of miR-142-5p/212-5p overexpression on the TP53INP1 protein level and the proliferation and collagen formation of CFs were reversed by c-Myc overexpression. Moreover, overexpression of miR-142-5p/212-5p improved cardiac function and collagen formation of MI mice. Overexpression of miR-142-5p/212-5p cooperatively suppresses the proliferation and collagen formation after MI by regulating c-Myc/TP53INP1.