LncRNA CRNDE inhibits cardiomyocytes apoptosis by YAP1 in myocardial ischaemia/reperfusion injury

Abstract

Background

Cardiomyocytes apoptosis is the basic pathological process of myocardial ischaemia/reperfusion (MI/R) injury, so inhibiting apoptosis of cardiomyocytes can effectively improve MI/R injury. Long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) can inhibit cell apoptosis, but its specific role in MI/R injury has not been studied. The aim of this study is to explore the specific effect of lncRNA CRNDE on cardiomyocytes apoptosis.

Methods

MI/R model in vivo and hypoxia/re-oxygenation (H/R) model in vitro were constructed. Apoptotic levels were assessed by TUNEL staining assay. QRT-PCR was used to validate lncRNA CRNDE level in myocardial tissues and HL-1 cells. The protein expressions of YAP1, Bcl-2 and cleaved caspase-3 were detected by western blot analysis. Flow cytometry was used to determine the apoptosis rate of cardiomyocytes. RIP assay was used to detect the interaction between lncRNA CRNDE and YAP1.

Results

The extent of cardiomyocytes apoptosis was significantly increased, and the levels of lncRNA CRNDE, YAP1 and Bcl-2 were down-regulated, while cleaved caspase-3 expression was up-regulated in MI/R mice and H/R-treated HL-1 cells. The expressions of YAP1 and Bcl-2 were decreased, while the expression of cleaved caspase-3 was increased after the knockdown of lncRNA CRNDE. Furthermore, lncRNA CRNDE could bind to YAP1 and regulated the protein level of YAP1 by ubiquitination and proteasomal degradation pathway. After transfection of Si-YAP1 in the H/R-treated HL-1 cells transfected with pc-DNA CRNDE, the protein level of Bcl-2 was decreased, while cleaved caspase-3 expression and the apoptosis rate were increased.

Conclusion

Our study suggested that lncRNA CRNDE could regulate YAP1 level by ubiquitination and proteasomal degradation pathway, thus inhibiting cardiomyocytes apoptosis in MI/R injury.

Keywords:

• Myocardial ischaemia/reperfusion injury
• lncRNA CRNDE
• YAP1
• cardiomyocytes apoptosis

Disclosure statement

All authors declare that there is no conflict of interest.

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.