MiR‐590‐3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1

Abstract

Previous studies have implicated the attractive and promising role of miR‐590‐3p to restore the cardiac function following myocardial infarction (MI). However, the molecular mechanisms for how miR‐590‐3p involves in cardiac fibrosis remain largely unexplored. Using human cardiac fibroblasts (HCFs) as the cellular model, luciferase report assay, mutation, EdU assay and transwell migration assay were applied to investigate the biological effects of miR‐590‐3p on the proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts. We found that miR‐590‐3p significantly suppressed cell proliferation and migration of HCFs. The mRNA and protein expression levels of α‐SMA, Col1A1 and Col3A were significantly decreased by miR‐590‐3p. Moreover, miR‐590‐3p directly targeted at the 3’UTR of ZEB1 to repress the translation of ZEB1. Interfering with the expression of ZEB1 significantly decreased the cell proliferation, migration activity, mRNA and protein expressions of α‐SMA, Col1A1 and Col3A. Furthermore, the expressions of miR‐590‐3p and ZEB1 were identified in infarct area of MI model in pigs. Collectively, miR‐590‐3p suppresses the cell proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts by targeting ZEB1. These works will provide useful biological information for future studies on potential roles of miR‐590‐3p as the therapeutic target to recover cardiac function following MI.

Long noncoding RNA LINC01615 promotes keloid development via sponging miR-590-3p to regulate FGF2 expression

“…However, the role of miR-590-3p in keloid is unclear. A previous study reported that miR-590-3p inhibited cardiac fibroblasts progression [16]. Consistent with this, we also proved the inhibitory effect of miR-590-3p in keloid fibroblasts.…”

“…On the other hand, it also can play a tumor-promoting action in colorectal cancer and ovarian cancer [14,15]. Moreover, miR-590-3p represses the progression of cardiac fibroblasts [16].…”

MiR‐590‐3p regulates cardiomyocyte P19CL6 proliferation, apoptosis and differentiation in vitro by targeting PTPN1 via JNK/STAT/NF‐kB pathway

“…miR-590-3p could regulate proliferation, migration and collagen synthesis of cardiac fibroblasts by targeting ZEB1. 19 The rapid delivery of miR-590-3p using targeted exosomes can be used as a potential therapeutic phenomenon to treat acute myocardial infarction. 20 miR-590-3p is capable of inducing proliferation of cardiomyocytes and cardiac regeneration.…”

Impact of chronic intermittent hypoxia on the long non‐coding RNA and mRNA expression profiles in myocardial infarction

“…Further investigation based on the lncRNA‐mRNA expression correlation network analysis to predict the possible mechanism of these lncRNAs revealed that both NONMMUT032513 and NONMMUT074571 were significantly associated with genes involved in the pathology of MI. For instance, ZEB1, which is positively linked to NONMMUT032513 and NONMMUT074571 in our findings, has been identified as an extremely abundant protein in the infarct area of MI models 43 . The high expression of ZEB1 promotes cardiac fibrosis, stabilizes collagen and aggravates MI by suppressing CXCR4 and increasing the level of collagen cross‐linking enzymes, Col1A1 and Col3A1 44,45 .…”

“…For instance, ZEB1, which is positively linked to NONMMUT032513 and NONMMUT074571 in our findings, has been identified as an extremely abundant protein in the infarct area of MI models. 43 The high expression of ZEB1 promotes cardiac fibrosis, stabilizes collagen and aggravates MI by suppressing CXCR4 and increasing the level of collagen cross-linking enzymes, Col1A1 and Col3A1. 44,45 Moreover, the clinical outcome after MI is highly correlated with NF-κB, interleukin (IL)-6…”