J Thromb Thrombolysis. 2022 Jan;53(1):136-148. doi: 10.1007/s11239-021-02540-1. Epub 2021 Aug 5.

Overexpression of miR-1298 attenuates myocardial ischemia-reperfusion injury by targeting PP2A

Chun Ouyang  1 Lei Huang  1 Xiaoqiang Ye  1 Mingming Ren  2 Zhen Han  3 Affiliations

Abstract

Previous studies reported that microRNA-1298 was abnormally expressed in the myocardium of rat hearts after hypoxia/normoxia injury. This study aims to investigate the function and specific mechanism of miR-1298 in myocardial ischemia/reperfusion (IR) injury. Neonatal rat cardiomyocytes (NRCMs) were isolated from neonatal rat hearts and subjected to oxygen/glucose deprivation/reperfusion (OGD/R) to induce I/R injury. The rat model with I/R injury was induced by ligating the proximal left anterior descending artery (LAD). MiR-1298 expression was detected by qRT-PCR. The levels of PP2A, Bcl-2, Bax, and AMPK signaling members (p-AMPK, p-GSK3β) was detected by Western blot. Cell apoptosis was evaluated by TUNEL staining assay and flow cytometry. The infarct size of rat hearts was assessed by TTC staining assay. Premature and mature MiR-1298 were significantly downregulated while PP2A was significantly upregulated during I/R injury both in vitro and in vivo. The prediction of Starbase suggested that PP2A was a potential target of miR-1298. MiR-1298 overexpression significantly reduced cardiomyocyte apoptosis in vitro, and its protective effect was obviously attenuated by PP2A overexpression. Luciferase reporter assay showed that miR-1298 targeted PP2A directly. In addition, miR-1298 overexpression significantly reduced infarct size and cardiomyocyte apoptosis in the hearts of rats received with I/R injury in vivo. Moreover, miR-1298 overexpression significantly elevated the levels of Bcl-2 and AMPK signaling members (p-AMPK, p-GSK3β) while decreased Bax level, and these effects were partially reversed by PP2A overexpression. MiR-1298 participated in myocardial I/R injury by targeting the PP2A/AMPK/GSK3β signaling pathway, suggesting that miR-1298 might be a potential therapeutic target for myocardial I/R injury.

Keywords: AMPK signaling; Apoptosis; Ischemia–reperfusion; PP2A; miR-1298.

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