Abnormal expression of miR-331 leads to impaired heart function.

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-331-5p 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.