Circ_0010729 knockdown protects cardiomyocytes against hypoxic dysfunction via miR-370-3p/TRAF6 axis

Authors

  • Jingjing Zhang Coronary Care Unit, Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou City, Henan Procince, China
  • Chuanyu Gao Department of Cardiology, People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Jinshui District, Zhengzhou 450003, Henan Procince, China; Tel: +86 0371-58680639, Fax: +86 0371-58680639; E-mail: gaochuanyuz@163.com
  • Jing Zhang Coronary Care Unit, Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou City, Henan Procince, China
  • Famin Ye Coronary Care Unit, Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou City, Henan Procince, China

DOI:

https://doi.org/10.17179/excli2020-2809

Keywords:

circ_0010729, miR-370-3p, TRAF6, cardiomyocytes, hypoxia

Abstract

Few studies have addressed the mechanism by which circ_0010729 regulates hypoxia-induced cell injury in cardiovascular diseases. However, its role and its regulatory mechanism in myocardial infarction remain to be explored. Cell viability, cycle, apoptosis, and migration were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity assay kit and transwell assay, respectively. Tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were examined by enzyme-linked immunosorbent assay. Glucose metabolism was calculated by detecting ATP production, glucose uptake and lactate production. Levels of circ_0010729, miR-370-3p and TNF Receptor Associated Factor 6 (TRAF6) were detected using quantitative real-time polymerase chain reaction or western blot. The direct interaction between circ_0010729 and TRAF6 or miR-370-3p was verified using dual-luciferase reporter assay and RNA immunoprecipitation assay. Under hypoxia condition, cardiomyocytes suffered from cell viability suppression, cell cycle arrest, cell apoptosis promotion, migration reduction, increase of inflammatory factor IL-6 and TNF-α, as well as glycolysis inhibition. Circ_0010729 expression was up-regulated in the cardiomyocytes at different hypoxia-exposed time points. Circ_0010729 knockdown protected cardiomyocytes against hypoxic dysfunction, while circ_0010729 overexpression showed inverse effects. MiR-370-3p was confirmed to directly bind to circ_0010729 or TRAF6. MiR-370-3p inhibition attenuated the protective effects of circ_0010729 knockdown on hypoxia-modulated cardiomyocyte dysfunction. MiR-370-3p restoration protected cardiomyocytes against hypoxic injury via targeting TRAF6. Besides, circ_0010729 indirectly regulated TRAF6 expression via miR-370-3p. This study demonstrated that circ_0010729 knockdown attenuated hypoxia-induced cardiomyocyte dysfunction via miR-370-3p/TRAF6 axis, indicating a potential therapeutic target for myocardial infarction.

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Published

2020-11-11

How to Cite

Zhang, J., Gao, C., Zhang, J. ., & Ye, F. . (2020). Circ_0010729 knockdown protects cardiomyocytes against hypoxic dysfunction via miR-370-3p/TRAF6 axis . EXCLI Journal, 19, 1520–1532. https://doi.org/10.17179/excli2020-2809

Issue

Vol. 19 (2020)

Section

Original articles

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Copyright (c) 2020 Jingjing Zhang, Chuanyu Gao, Jing Zhang, Famin Ye

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