Knockdown of KCNQ1OT1 attenuates cardiac hypertrophy through modulation of the miR-2054/AKT3 axis.

Abstract

BackgroundPersistent cardiac hypertrophy threatens health worldwide. Long non-coding RNAs (lncRNAs) attracted lots of attention in cardiac diseases such as cardiac hypertrophy. In this study, we aimed to study the function of KCNQ1OT1 in cardiac hypertrophy.MethodsWe first used qRT-PCR to detect the expression of KCNQ1OT1 in Ang-II-induced cardiomyocytes and mouse cardiac hypertrophy models. The function of KCNQ1OT1 was investigated by a loss-of-function test. Analysis of the luciferase reporter gene and RNA pulldown confirmed the interaction between KCNQ1OT1 and miR-2054. The target gene of miR-2054 was predicted by bioinformatics analysis and confirmed by luciferase reporter gene detection. Rescue experiments were performed to evaluate the role of miR-2054/AKT3 in the function of KCNQ1OT1.ResultsOur results suggested that KCNQ1OT1 was up-regulated in Ang-II-induced cardiomyocytes and transverse aortic constriction (TAC) mice. Knocking down of KCNQ1OT1 can reduce cell size and downregulate the expression of ANF, BNP and α-MHC in response to Ang-II. KCNQ1OT1 has been shown to compete competitively with miR-2054 and has a negative correlation with its expression. The combination of miR-2054 can reverse the effect of the KCNQ1OT1 combination in Ang-II-induced cardiomyocytes. In addition, AKT3 is a target of miR-2054 and mediates its effect on Ang-II-induced cardiomyocytes.ConclusionsKnockdown of KCNQ1OT1 could attenuate cardiac hypertrophy through modulation of the miR-2054/AKT3 axis.