YB1 protects cardiac myocytes against H2O2‑induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3

Wang,Shiqi; He,Fuwei; Li,Zhenwei; Hu,Yewen; Huangfu,Ning; Chen,Xiaomin

doi:10.3892/mmr.2019.10119

YB1 protects cardiac myocytes against H2O2‑induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3

Authors:
- Shiqi Wang
- Fuwei He
- Zhenwei Li
- Yewen Hu
- Ning Huangfu
- Xiaomin Chen
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Affiliations: Department of Cardiology, The Affiliated Hospital Ningbo No. 1 Hospital, Zhejiang University, Ningbo, Zhejiang 315000, P.R. China
Published online on: April 3, 2019 https://doi.org/10.3892/mmr.2019.10119
Pages: 4579-4588
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidative stress serves important roles in cardiac injury during the process of ischemia/reperfusion (I/R). Y‑box protein 1 (YB1), a member of the highly conserved Y‑box protein family, is closely associated with inflammation and stress responses by regulating gene transcription, RNA splicing and mRNA translation. However, the roles of YB1 in oxidative stress‑induced myocardial‑I/R (M‑I/R) injury are unknown. The aim of the present study was to examine the effects of YB1 on H2O2‑induced cardiomyocyte injury and its underlying mechanism. The results demonstrated that YB1 expression was upregulated during H2O2‑induced myocardial injury. YB1 knockdown through transfection of small interfering RNA significantly aggravated cardiac cell apoptosis. Furthermore, YB1 knockdown significantly reversed the H2O2‑mediated increase in phosphorylated signal transducer and activator of transcription (STAT)3, but did not affect the phosphorylation of P38, extracellular signal‑regulated kinases 1/2, c‑Jun N‑terminal kinases, P65, Janus kinase 1 and 2 or STAT1. Moreover, protein co‑immunoprecipitation and RNA‑binding protein immunoprecipitation assays revealed that YB1 interacted with protein inhibitor of activated STAT 3 (PIAS3) mRNA but not its translated protein. YB1 overexpression may have promoted PIAS3 mRNA decay, decreasing PIAS3 protein levels, and therefore increased the levels of phosphorylated STAT3. Finally, YB1 knockdown, mediated by a lentivirus carrying YB1 targeted short hairpin RNA, significantly decreased left ventricle percentage fractional shortening and ejection fraction values, while increasing the infarct sizes in a rat model of M‑I/R injury. These results demonstrated for the first time (to the best of our knowledge) that YB1 may protect cardiac myocytes against H2O2 or M‑I/R‑induced injury by binding to PIAS3 mRNA and resulting in the phosphorylation of STAT3.

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