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

Abstract

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.

miR‐8485 alleviates the injury of cardiomyocytes through TP53INP1

“…For example, in a mice model with myocardial infarction, inhibition of miR‐142‐5p, improves left ventricular function, reduces infarct size and collagen deposition, and inhibits the proliferation and differentiation of cardiac fibroblast into myofibroblasts via regulating TP53INP1. [ 25 ] Similarly, in another study, TP53INP1 is identified as a target of miR‐142‐5p in vitro, and TP53INP1 overexpression inhibits the activation of PI3K/AKT and MEK/ERK signaling pathways and aggravates the injury of cardiomyocytes. [ 12 ] Additionally, miR‐155 in cardiac fibroblasts targets TP53INP1 to repress cardiac remodeling.…”

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

“…TLR4 [500], ABCA1 [501], CCR2 [502], LDLR (low density lipoprotein receptor) [503], SIRT1 [504] and NOD2 [505] might crucially contribute to the development of hypercholesterolemia. ABCA1 [506], TLR5 [507], PTGS2 [508], TGFA (transforming growth factor alpha) [509], PDK4 [510], JAK2 [511], TLR2 [512], NEK7 [513], CCR1 [514], BACH1 [515], NCOA4 [195], LATS2 [516], PELI1 [517], EGR1 [518], CYBB (cytochrome b-245 beta chain) [519], MEFV (MEFV innate immuity regulator, pyrin) [520], CLEC4E [521], GCLC (glutamate-cysteine ligase catalytic subunit) [522], KLF3 [523], TP53INP1 [524], ITGB1 [525], IRF9 [526], PHLPP1 [527], NOD2 [528], ACSL4 [529], FGL2 [530], PF4 [531], VEGFB (vascular endothelial growth factor B) [532], CCR7 [533], IGFBP4 [534], TRPM4 [535], BAG1 [536], LGALS3 [537] and ATAD3A [538] could induce ischemic heart disease. Therefore, the data suggest that the identified DEGs which enriched in GO terms and pathways might participant in the development of CAD and its associated complications, and contribute to CAD and CAD related complications treatment.…”

Long Noncoding RNA Small Nuclear RNA Host Gene 7 Knockdown Protects Mouse Cardiac Fibroblasts Against Myocardial Infarction by Regulating miR-455-3p/Platelet-Activating Factor Receptor Axis

“…For MI model establishment, mice were subjected to occlusion of the left coronary artery. 24 In brief, mice were intraperitoneally inoculated with phenobarbital sodium (50 mg/kg) for anesthetization. After left intercostal thoracotomy, the left anterior descending coronary artery was ligated using sterile nylon suture, followed by validation of heart infarct through obvious S-T elevation in electrocardiograph and defective cyanotic cardiac muscle.…”