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Inflammation Research

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01-07-2020 | Heart Failure | Original Research Paper

LncRNA promoted inflammatory response in ischemic heart failure through regulation of miR-455-3p/TRAF6 axis

Authors: Qianqian Gu, Bin Wang, Hongying Zhao, Wenjuan Wang, Pengsheng Wang, Yu Deng

Published in: Inflammation Research | Issue 7/2020

Abstract

Objectives

Ischemic heart failure (IHF) is the most common cause of death globally. Growing evidence shows abnormal expression of long non-coding RNAs in heart failure patients. This study aims to investigate the effect of sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2-OT) on the regulation of the inflammatory response in ischemic heart failure.

Methods

IHF rat and oxygen and glucose deprivation (OGD) cell models were established. qRT-PCR was employed to investigate the expression of SOX2-OT. ELISA, western blot and cell viability/apoptosis assays were performed to assess the effects of SOX2-OT. Online software program was used to identify miRNAs that target SOX2-OT, followed by validation using RNA pull-down. Potential targets of miRNAs were searched, and examined by immunoblotting, qRT-PCR and luciferase reporter assay.

Results

SOX2-OT was up-regulated in IHF and OGD. Knockdown of SOX2-OT promoted cell proliferation, decreased apoptosis rate and cell oxidative damage, and ameliorated inflammatory response. SOX2-OT contains binding sites for miR-455-3p, miR-5586-3p and miR-1252-5p. RNA pull-down confirmed the binding ability between SOX2-OT and miR-455-3p. TRAF6 is a direct target of miR-455-3p. Moreover, the regulatory activity of SOX2-OT on inflammatory response was partially through its negative regulation of miR-455-3p, which directly regulates TRAF6. Down-regulation of SOX2-OT improved myocardial dysfunction in IHF rat.

Conclusions

Our results reveal that SOX2-OT may be a driver of IHF through repression of miR-455-3p, and miR-455-3p alleviates IHF by targeting TRAF6. Therefore, SOX2-OT/miR-455-3p/TRAF6 may be a potential target for advanced therapeutic strategy for IHF.

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Title: LncRNA promoted inflammatory response in ischemic heart failure through regulation of miR-455-3p/TRAF6 axis
Authors: Qianqian Gu
Bin Wang
Hongying Zhao
Wenjuan Wang
Pengsheng Wang
Yu Deng
Publication date: 01-07-2020
Publisher: Springer International Publishing
Keyword: Heart Failure
Published in: Inflammation Research / Issue 7/2020
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-020-01348-8

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