piRNA-6426 increases DNMT3B-mediated SOAT1 methylation and improves heart failure

piRNA-6426 overexpression inhibits hypoxia-induced cardiomyocyte dysfunction and HF by promoting DNMT3B-mediated methylation of SOAT1 promoter.

The level of piRNA-6426 in the venous blood of HF patients and volunteers was detected by RT-qPCR. Hypoxia-induced cardiomyocytes were transfected with lentiviral-mediated piRNA-6426 overexpression vector (LV-piRNA-6426) or together with LV-DNMT3B, and then cell viability and apoptosis, glucose uptake, ROS production, LDH activity and secretion of inflammatory factors were detected. Also, cardiomyocytes were transfected with LV-piRNA-6426, sh-piRNA-6426 or sh-SOAT1, as well as LV-piRNA-6426 or together with LV-DNMT3B or sh-DNMT3B. The interaction between piRNA-6426 and methyltransferase 3B (DNMT3B) was detected with RNA immunoprecipitation (RIP). And the methylation level of sterol o-acyltransferase 1 (SOAT1) and the enrichment of DNMT3B in the SOAT1 promoter were detected with Methylation-specific PCR (MSP) and ChIP assays. Then a HF rat model constructed with coronary artery occlusion method was injected with LV-piRNA-6426, and heart function index and infarcted area of rat heart were detected.

Previous studies found that piRNAs could participate in disease progression by regulating DNA methylation, but there are few reports on their roles in heart failure (HF).

piRNA-6426 expression was decreased in the blood of HF patients. LV-piRNA-6426 transfection increased the enrichment of DNMT3B in SOAT1 promoter, thereby inhibiting the expression level of SOAT1, and decreased hypoxia-induced oxidative stress and inflammation in cardiomyocytes, while sh-piRNA-6426 transfection had the opposite effect. And LV-DNMT3B transfection enhanced the effect of LV-piRNA-6426 transfection on SOAT1 expression and cardiomyocyte dysfunction. Injection of LV-piRNA-6426 significantly inhibited the heart dysfunction of rats. Conclusions: piRNA-6426 overexpression inhibits hypoxia-induced cardiomyocyte dysfunction and HF by promoting DNMT3B-mediated methylation of SOAT1 promoter.