LncRNA KCNQ1OT1 attenuates sepsis-induced myocardial injury via regulating miR-192-5p/XIAP axis.

UNLABELLED

Myocardial dysfunction is a prime cause of death in sepsis. This study is to delve into the function of lncRNA KCNQ1OT1 in myocardial injury induced by sepsis. Sepsis-induced myocardial injury model in rat was initiated by intraperitoneally injecting of LPS (10 mg/kg) , and cardiomyocyte H9c2 was treated with LPS to mimic sepsis KCNQ1OT1 and miR-192-5p expressions were detected by qRT-PCR. The cell viability was probed with CCK-8 experiment and the apoptosis of the cardiomyocytes was tested using flow cytometry analysis. Western blot was operated to determine apoptosis-related proteins expressions. ELISA was used to evaluate the levels of TNF-α, IL-6, and IL-1β. Bioinformatics analysis, RT-PCR, dual luciferase reporter assay, and RNA immunoprecipitation experiment were utilized to detect the interrelation of genes. Herein, we proved that KCNQ1OT1 was considerably down-regulated, whereas miR-192-5p was markedly increased in myocardial tissues of septic rats. KCNQ1OT1 interrelated with miR-192-5p, and negatively modulated its expression levels. Overexpression of KCNQ1OT1 or the transfection of miR-192-5p inhibitors greatly facilitated the viability and impeded the apoptosis of H9c2 cardiomyocytes. miR-192-5p paired with the 3ʹUTR of XIAP, and repressed its protein expression, and XIAP was modulated positively by KCNQ1OT1. In conclusion, our work indicates that down-regulation of KCNQ1OT1 advances cardiac injury through regulating miR-192-5p/XIAP axis during sepsis.

IMPACT STATEMENT

Sepsis-induced cardiomyopathy remains to be a major challenge to health care systems around the globe. There are no known therapies currently available that can cure the disease. This study provides convincing evidence that KCNQ1OT1 could attenuate sepsis-mediated myocardial injury. We further demonstrate that the beneficial function of KCNQ1OT1 was achieved by regulating the miR-192-5p/XIAP axis. We therefore found a new mechanism of cardioprotective effect of KCNQ1OT1, one which also offers a novel theoretical basis for the therapy of sepsis-induced cardiomyopathy.