Protective role of long noncoding RNA CRNDE in myocardial tissues from injury caused by sepsis through the microRNA-29a/SIRT1 axis

Aims: The associations between colorectal neoplasia differentially expressed (CRNDE), a novel long non-coding RNA (lncRNA), and inflammation and cell apoptosis have been underscored recently. However, its function in sepsis-induced myocardial injury remains undetermined. The current study sets to examine the putative mechanism of CRNDE in myocardial injury evoked by sepsis. Materials and methods: Firstly, the rat model of sepsis was developed and verified. Subsequently, differentially expressed lncRNAs in myocardial tissues of septic rats were determined. Afterwards, CRNDE overexpression or knockdown was introduced into the myocardial tissues of rats. Then, H9c2 cells were induced by lipopolysaccharide (LPS) and transfected with overexpression of CRNDE and sirtuin 1 (SIRT1), si-CRNDE or microRNA (miR)-29a mimic. Apoptosis, Caspase-3 activity, secretion of inflammatory factors, and intracellular reactive oxygen species (ROS) content were subsequently measured in rat tissues and transfected cells. Finally, the NF-κB/PARP-1 signaling activity in rat myocardial tissues and cells was detected. Key findings: CRNDE expression was reduced in the myocardial tissues of rats with sepsis, and CRNDE restoration alleviated following myocardial injury. Additionally, overexpression of CRNDE inhibited cardiomyocyte apoptosis, ROS content, Caspase-3 activity, nuclear NF-κB p65 phosphorylation and PARP-1 expression. Dual-luciferase assays showed that the CRNDE/miR-29a/SIRT1 network regulated sepsis-induced myocardial injury. Moreover, miR-29a mimic attenuated the protective effect of CRNDE overexpression on LPS-induced cardiomyocytes. Significance: CRNDE protects the myocardial tissues against sepsis-induced cardiomyocyte apoptosis and oxidative damage by inhibiting the post-transcriptional regulatory function of miR-29a on SIRT1.