Abnormal expression of miR-331 leads to impaired heart function

• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2019,（14）
• 页码范围: 1011-1017
• 页数: 7页
• 语种: 英文

摘要

MicroRNAs (miRNAs) play important roles in maintaining normal heart function.Abnormal expression of miR-331 has been observed in the hearts of patients with atrial fibrillation and Marfan syndrome.However,whether miR-331 regulates cardiac function under physiological and pathological conditions still remains unknown.In the present study,we investigated the function and underlying mechanisms of miR-331 in a pressure overload-induced heart failure model and miR-331 transgenic rat model.First,we found that the expression of miR-331-3p exhibited a 1.7-fold increase in hypertrophy compared with that in the sham group (P＜0.01),yet the expression of miR-331-Sp remained unchanged.Furthermore,overexpression of miR-331 in cardiomyocytes and defective excitation-contraction (E-C) coupling efficiency were observed.Luciferase assays showed that miR-331-3p suppressed JPH2 expression by binding to the coding region of JPH2 mRNA.Finally,in the miR-331 transgenic rat model,JPH2 expression was suppressed at both the mRNA and protein levels in vivo,which resulted in impairment of both the E-C coupling efficiency of cardiomyocytes and systolic function of the heart.This finding mechanistically linked miR-331 to JPH2 downregulation and suggested an important role for the abnormal expression of miR-331 leading to the dysfunction of E-C coupling in heart failure.