17 August 2017 : Laboratory Research
Role of MicroRNA-93 I in Pathogenesis of Left Ventricular Remodeling via Targeting Cyclin-D1
Jingjing Zhang1BCDEF, Li Qin1BCF, Ling Han1ABCDEFG*, Ying Zhao2BDF, Hongfeng Jing3CEF, Wei Song4ADEF, Haili Shi1BEFDOI: 10.12659/MSM.897542
Med Sci Monit 2017; 23:3981-3988
Abstract
BACKGROUND: The objective of this study was to identify the pathway responsible for ventricular remodeling.
MATERIAL AND METHODS: We collected remodeling myocardium tissue (n=18) and control myocardium tissue (n=22), and detected the expression of 4 miRNAs in these 2 groups using real-time PCR. We then searched the miRNA database online to find the candidate genes of miR-93. Real-time PCR and Western blot analysis were used to confirm the regulatory relationship.
RESULTS: We found that only miR-93 was decreased in remodeling myocardium tissue, and validated CCND1 to be the direct target gene of miR-93, with the “seed sequence” located within the 3’-UTR of the target gene via luciferase reporter assay system. Furthermore, we established the negative regulatory relationship between miR-93 and CCND1 by determining the relative luciferase activity of cells transfected with wild-type or mutant 3’-UTR of CCND1. We also found that The CCND1 protein and mRNA expression level of HL-1 cells treated with 50 nM miR-93 mimics were apparently lower than the scramble control, and those of the cells treated with 100 nM miR-93 mimics and CCND1 siRNA (100 nM) were even lower than those in the 50 nM treatment group. Meanwhile, cells transfected with miR-93 mimics (50 nM) showed evidently downregulated viability when compared with the scramble controls, while cells transfected with (100 nM) and CCND1 siRNA (100nM) showed even lower viability.
CONCLUSIONS: We showed that CCND1 is a direct target of miR-93, and the dysregulation of the miR-93/CCND1 signaling pathway is responsible for the development of ventricular remodeling.
Keywords: Ventricular Remodeling
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