Role of MicroRNA-93 I in Pathogenesis of Left Ventricular Remodeling via Targeting Cyclin-D1
| Autor: | Wei Song, Jingjing Zhang, Haili Shi, Ling Han, Li Qin, Ying Zhao, Hongfeng Jing |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Untranslated region Male medicine.medical_specialty Down-Regulation Apoptosis Real-Time Polymerase Chain Reaction Cell Line 03 medical and health sciences 0302 clinical medicine Cyclin D1 Lab/In Vitro Research Internal medicine microRNA medicine Humans Luciferase Ventricular remodeling 3' Untranslated Regions Cell Proliferation Ventricular Remodeling Chemistry Myocardium Cell Cycle General Medicine Transfection Middle Aged medicine.disease Cell biology MicroRNAs 030104 developmental biology Real-time polymerase chain reaction Cell culture 030220 oncology & carcinogenesis Cardiology Female Signal Transduction |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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