LncRNA KCNQ1OT1 contributes to cardiomyocyte apoptosis by targeting FUS in heart failure.

Abstract Long noncoding RNAs (lncRNAs) have recently been recognized as the important regulators in cardiac diseases. This study was aimed to investigate the role and molecular mechanism of lncRNA KCNQ1OT1 in regulating cardiomyocyte apoptosis in heart failure (HF). The mouse model of HF was induced by doxorubicin (ADR). Cell apoptosis was detected by Hoechst and TUNEL staining. Molecule expressions were determined by qRT-PCR and western blot. The interaction between KCNQ1OT1 and Fused in sarcoma (FUS) was assessed by RNA immunoprecipitation (RIP) and RNA pull-down assay. KCNQ1OT1 was up-regulated in the myocardial tissues of HF mice and the ADR-stimulated mouse cardiomyocyte line (HL−1). KCNQ1OT1 overexpression promoted apoptosis of ADR-stimulated HL-1 cells, while KCNQ1OT1 knockdown caused the opposite effect. The RIP and RNA pull-down results showed that KCNQ1OT1 directly bound with FUS and negatively regulated its protein level. Knockdown of FUS inhibited apoptosis of ADR-stimulated HL-1 cells and reversed the effect of KCNQ1OT1 overexpression on cardiomyocyte apoptosis. In vivo experiment showed that KCNQ1OT1 improved myocardial histopathological changes, reduced myocardial fibrosis areas, down-regulated FUS expression, and inhibited cell apoptosis of HF mice. In conclusion, KCNQ1OT1 facilitates cardiomyocyte apoptosis by directly targeting FUS in ADR-induced HF.