1. Academic Validation
  2. CircRbms1 fosters MST1 mRNA and protein levels to motivate myocardial ischaemia-reperfusion injury via autophagic status

CircRbms1 fosters MST1 mRNA and protein levels to motivate myocardial ischaemia-reperfusion injury via autophagic status

  • ESC Heart Fail. 2024 Jan 30. doi: 10.1002/ehf2.14673.
Qin Liu 1 Guorong Lai 2 Yanhui Hu 1 Fan Yang 2 Chao Zhang 2 Dongsheng Le 2 Fumou Deng 1 Xianliang Xing 1 Binquan Tang 1 Huanhuan Jie 3 Yingping Liang 2 Enjun Lei 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 2 Department of Pain Management, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 3 Department of Anesthesiology, Ganzhou People's Hospital, Ganzhou, China.
  • 4 Department of Anesthesiology, First Affiliated Hospital of Nanchang University, Nanchang, China.
Abstract

Aims: Acute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia-reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury.

Methods and results: An in vivo MI mice model and an in vitro MI cell model was established. The expression levels were detected using quantitative Real-Time PCR (qRT-PCR) and western blot. Cellular proliferation, Apoptosis, Pyroptosis, and Autophagy were detected by immunostaining, immunohistochemistry, western blot, and transmission electron microscopy (TEM). Dual-luciferase reporter assay, RNA pull-down assay, and RIP assay were performed to validate the molecular interactions. CircRbms1 was up-regulated in A/R-induced HCMs and acted as a Sponge for miR-142-3p, thereby targeting MST1. CircRbms1 could improve stability of MST1 by recruiting IGF2BP2 (all P < 0.05). CircRbms1 knockout reduced cell Pyroptosis, improved Autophagy and proliferation level in A/R-induced HCMs (all P < 0.05). CircRbms1 knockout alleviated cardiac dysfunction and cell Pyroptosis and enhanced Autophagy and proliferation in mice through the miR-142-3p/MST1 axis.

Conclusions: CircRbms1 inhibited the miR-142-3p/MST1 axis and played a protective role in myocardial I/R injury. It may provide a new therapeutic target for I/R heart injury.

Keywords

Autophagy; MST1; Myocardial injury; Pyroptosis; circRbms1; miR-142-3p.

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