miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11.

Abstract

Necroptosis has been discovered as a new paradigm of cell death and may play a key role in heart disease and selenium (Se) deficiency. Hence, we detected the specific microRNA (miRNA) in response to Se-deficient heart using microRNAome analysis. For high-throughput sequencing using Se-deficient chicken cardiac tissue, we selected miR-200a-5p and its target gene ring finger protein 11 (RNF11) based on differential expression in cardiac tissue and confirmed the relationship between miR-200a-5p and RNF11 by dual luciferase reporter assay and real-time quantitative PCR (qRT-PCR) in cardiomyocytes. We further explored the function of miR-200a-5p and observed that overexpression of miR-200a-5p spark the receptor interacting serine/threonine kinase 3 (RIP3)-dependent necroptosis in vivo and in vitro. To understand whether miR-200a-5p and RNF11 are involved in the RIP3-dependent necroptosis pathway, we presumed that oxidative stress, inflammation response and the mitogen-activated protein kinase (MAPK) pathway might trigger necroptosis. Interestingly, necroptosis trigger, z-VAD-fmk, failed to induce necroptosis but enhanced cell survival against necrosis in cardiomyocytes with knockdown of miR-200a-5p. Our present study provides a new insight that the modulation of miR-200a-5p and its target gene might block necroptosis in the heart, revealing a novel myocardial necrosis regulation model in heart disease.

• Authors: Tianshu Yang, Changyu Cao, Jie Yang, Tianqi Liu, Xin Gen Lei, Ziwei Zhang, Shiwen Xu
• Journal: Redox biology (Redox Biol) Vol. 15 Pg. 159-169 (05 2018) ISSN: 2213-2317 [Electronic] Netherlands
• PMID: 29248830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Carrier Proteins
• DNA-Binding Proteins
• MicroRNAs
• RNF11 protein, human
• Reactive Oxygen Species
• Selenium

Topics

• Animals
• Apoptosis (genetics)
• Carrier Proteins (genetics)
• Chickens (genetics, metabolism)
• DNA-Binding Proteins
• Humans
• MicroRNAs (genetics)
• Myocardial Reperfusion Injury (genetics, metabolism, pathology)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Necrosis (genetics, metabolism, pathology)
• Oxidative Stress (genetics)
• Reactive Oxygen Species (metabolism)
• Selenium (deficiency, metabolism)