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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 ?-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 ?-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.

SUBMITTER: Yuan X

PROVIDER: S-EPMC6933374 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Yuan Xiaolong X Pan Jinchun J Wen Lijuan L Gong Baoyong B Li Jiaqi J Gao Hongbin H Tan Weijiang W Liang Shi S Zhang Hao H Wang Xilong X

Journal of cellular and molecular medicine 20191101 1

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, ...[more]

PMID: 31675172

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Project description:Background:The occurrence of pathological cardiac fibrosis is attributed to tissue hypoxia. Circular RNAs play significant regulatory roles in multiple cardiovascular diseases and are involved in the regulation of physiological and pathophysiological processes. CircHIPK3 has been identified as the one of the most crucial regulators in cardiac fibrosis. However, the mechanisms by which circHIPK3 regulates cardiac fibrosis under hypoxia remain unclear. Our study aimed to determine circHIPK3 expression in cardiac fibroblasts (CFs) and investigate the functions of circHIPK3 in hypoxia environment. Methods:The expression level of circHIPK3 in CFs under hypoxia (1% O2) was analyzed by qRT-PCR. The role of circHIPK3 on the proliferation and migration of CFs were determined by EdU, cell wound scratch assay and cell cycle. The expression of proteins associated with phenotypic transformation in CFs in vitro was examined by immunofluorescence assay and western blot. Bioinformatics analysis, dual luciferase activity assay and RNA fluorescent in situ hybridization assay revealed that miR-152-3p was identified as a target of circHIPK3 and that TGF-?2 was targeted by miR-152-3p. Results:CircHIPK3 expression was significantly upregulated in CFs in a hypoxic environment. In vitro, overexpressing circHIPK3 obviously promoted CF proliferation, migration and phenotypic changes under hypoxia, but those processes were suppressed by circHIPK3 silencing. CircHIPK3 acted as an endogenous miR-152-3p sponge and miR-152-3p aggravated circHIPK3 silencing induced inhibition of CF proliferation, migration, phenotypic transformation and TGF-?2 expression in vitro. In summary, circHIPK3 plays a pivotal role in the development of cardiac fibrosis by targeting the miR-152-3p/TGF-?2 axis. Conclusions:These findings demonstrated that circHIPK3 acted as a miR-152-3p sponge to regulate CF proliferation, migration and phenotypic transformation through TGF-?2, revealing that modulation of circHIPK3 expression may represent a potential target to promote the transition of hypoxia-induced CFs to myofibroblasts.

Project description:Background: Increasing evidence suggested that microRNA and kinesin superfamily proteins play an essential role in ovarian cancer. The association between KIF4A and ovarian cancer (OC) was investigated in this study.Methods: We performed bioinformatics analysis in the GEO database to screen out the differentially expressed miRNAs (DEmiRNAs) associated with ovarian cancer prognosis. Upstream targeting prediction for KIF4A was acquired by using the mirDIP database. The potential regulatory factor miR-29c-3p for KIF4A was obtained from the intersection of the above all miRNAs. The prognosis of KIF4A and target-miRNA in OC was obtained in the subsequent analysis. qRT-PCR and Western blot detected KIF4A expression level in IOSE80 (human normal ovarian epithelial cell line). In the meantime, the gene expression level was detected in A2780, HO-8910PM, COC1, and SKOV3 cell lines (human ovarian carcinoma cell line). MTT and colony formation assays were used to detect cell proliferation of SKOV3 cell line. The following assays detected cell migration through the use of transwell and wound heal assays. Targeted binding relationship between KIF4A and miRNA was detected by using the dual-luciferase reporter assay.Results: Both high expression of KIF4A and lower expression of miR-29c-3p could be used as biomarkers indicating poor prognosis in OC patients. Cellular function tests confirmed that when KIF4A was silenced, it inhibited the proliferation and migration of OC cells. In addition, 3'-UTR of KIF4A had a direct binding site with miR-29c-3p, which indicated that the expression of KIF4A could be regulated by miR-29c-3p. In subsequent assays, the proliferation and migration of OC cells were inhibited by the overexpression of miR-29c-3p. At the same time, rescue experiments also confirmed that the promotion of KIF4A could be reversed by miR-29c-3p.Conclusion: In a word, our data revealed a new mechanism for the role of KIF4A in the occurrence and development of OC.

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

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

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