Mir-423-5p Inhibits Human Cardiomyoblast Proliferation And Induces Cell Apoptosis By Targeting Gab 1

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2016)

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摘要
Background: Dilated cardiomyopathy (DCM) is a heart disease characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure. MicroRNAs are important regulators of gene expression, influencing the progression of DCM. This study aimed to reveal the role of microRNA-423-5p (miR-423-5p) in human cardiomyoblast cell (HCM) and its potential mechanisms. Materials and methods: Serum samples were obtained from DCM patients and used to analyze miRNAs levels compared to healthy control. After transfected with miR-423-5p mimics in HCM cells or miR-423-5p mimics+ pcDNA3.1+HA-Gab 1, the functions of proliferation and apoptosis were investigated. Quantitative polymerase chain reaction analysis and western blot were performed to detect the expression of related proteins in HCM cells. The target gene of miR-423-5p was determined by luciferase assay and western blot. Results: The expression level of miR-423-5p was dramatically increased in DCM patients. Introduction of miR-4235p significantly suppressed the proliferation and induced apoptosis of HCM cells. Luciferase reporter assay identified the 3'-UTR of Grb2-associated binders 1 (Gab 1) mRNA contained a complementary sequence for miR-423-5p. Gab 1 re-introduction could reverse the anti-proliferation and pro-apoptosis role of miR-423-5p. Conclusions: Our study provided a better understanding of miR-423-5p function in DCM development, which may also be benefit for the development of miRNA-directed diagnostic and therapeutic against DCM.
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关键词
Dilated cardiomyopathy, microRNAs, human cardiomyoblast cell, Gab 1, proliferation, apoptosis
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