LncRNA HOX transcript antisense RNA mitigates cardiac function injury in chronic heart failure via regulating microRNA-30a-5p to target KDM3A.

Abstract

Long noncoding RNA HOX transcript antisense RNA (HOTAIR) has been studied in multiple diseases, but the role of HOTAIR on chronic heart failure (CHF) through the regulation of microRNA (miR)‐30a‐5p and lysine‐specific demethylase 3A (KDM3A) remains unexplored. This research aims to probe the effects of HOTAIR on CHF progression via modulating miR‐30a‐5p to target KDM3A. CHF mouse model was established by intraperitoneal injection of doxorubicin. The CHF mice were then injected with high‐expressed HOTAIR, miR‐30a‐5p or KDM3A adenovirus vectors to determine the cardiac function, oxidative stress, inflammatory response, pathological change and cardiomyocyte apoptosis. HOTAIR, miR‐30a‐5p, KDM3A and Bcl‐2/adenovirus E1B 19kDa interacting protein 3 (BNIP3) expression in CHF mice was detected. The binding relations among HOTAIR, miR‐30a‐5p and KDM3A were validated. HOTAIR and KDM3A were depleted, while miR‐30a‐5p was augmented in CHF mice. The elevated HOTAIR or KDM3A or could improve cardiac function, mitigate oxidative stress and pathological change, reduce inflammatory factor levels and cardiomyocyte apoptosis, while the increased miR‐30a‐5p exerted opposite effects. The miR‐30a‐5p elevation could reverse the effects of enriched HOTAIR, while BNIP3 reduction abrogated the effects of KDM3A on CHF. HOTAIR sponged miR‐30a‐5p that targeted KDM3A. HOTAIR improves cardiac injury in CHF via modulating miR‐30a‐5p to target KDM3A. This study provides novel therapeutic strategies for CHF treatment.