Identification of micro‐RNA networks in end‐stage heart failure because of dilated cardiomyopathy

Journal of Cellular and Molecular Medicine

Xiaoming Zhu²  Hongjiang Wang²  Fan Liu¹  Li Chen⁴  Weijia Luo³  Pixiong Su²  Weiming Li²  Liping Yu²  Xinchun Yang² 

[1] Center of Clinical Laboratory, Zhongshan Hospital, Medical College of Xiamen University, Xiamen, China;Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China;Center for Molecular Medicine and Experimental Therapeutics, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA;Stem Cell Engineering Laboratory, Texas Heart Institute, Houston, TX, USA

关键词: heart failure;    microRNAs;    network;   

DOI  :  10.1111/jcmm.12096

来源: Wiley

【 摘 要 】

Abstract

Micro-RNAs regulate gene expression by directly binding to the target mRNAs. The goal of the study was to examine the expression profiling of miRNAs in human failing hearts and identify the key miRNAs that regulate molecular signalling networks and thus contribute to this pathological process. The levels of miRNAs and expressed genes were analysed in myocardial biopsy samples from patients with end-stage heart failure (n = 14) and those from normal heart samples (n = 8). Four networks were built including the Gene regulatory network, Signal-Network, miRNA-GO-Network and miRNA-Gene-Network. According to the fold change in the network and probability values in the microarray cohort, RT-PCR was performed to measure the expression of five of the 72 differentially regulated miRNAs. miR-340 achieved statistically significant. miR-340 was identified for the first time in cardiac pathophysiological condition. We overexpressed miR-340 in cultured neonatal rat cardiomyocytes to identify whether miR-340 plays a determining role in the progression of heart failure. ANP, BNP and caspase-3 were significantly elevated in the miR-340 transfected cells compared with controls (P < 0.05). The cross-sectional area of overexpressing miR-340 cardiomyocytes (1952.22 ± 106.59) was greater (P < 0.0001) than controls (1059.99 ± 45.59) documented by Laser Confocal Microscopy. The changes of cellular structure and the volume were statistical significance. Our study provided a comprehensive miRNA expression profiling in the end-stage heart failure and identified miR-340 as a key miRNA contributing to the occurrence and progression of heart failure. Our discoveries provide novel therapeutic targets for patients with heart failure.

【 授权许可】

CC BY   
© 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.