Circular RNA circHIPK3 is downregulated in diabetic cardiomyopathy and overexpression of circHIPK3 suppresses PTEN to protect cardiomyocytes from high glucose-induced cell apoptosis

Abstract

ABSTRACT It has been reported that circHIPK3 can be downregulated by high glucose, suggesting its potential involvement in diabetes and diabetic complications. This study aimed to explore the role of circHIPK3 in diabetic cardiomyopathy (DC). PTEN is a kind of tumor suppressor gene, which is very commonly lost in human cancer. We detected the expression of circHIPK3 and PTEN in plasma samples from DC patients, diabetic patients without complications diabetes mellitus (DM) and health controls by RT-qPCR and ELISA. In vitro cell experiment, AC16 cells (cardiomyocytes) were treated with high glucose, followed by expression analysis of circHIPK3 and PTEN mRNA by RT-qPCR. CircHIPK3 or PTEN expression vector were used to overexpress circHIPK3 and PTEN in AC16 cells to explore the relationship between them. The role of circHIPK3 and PTEN in regulating the apoptosis of AC16 cells was analyzed by cell apoptosis assay. The result showed that CircHIPK3 was downregulated in diabetes and further downregulated in DC. In AC16 cells, high glucose treatment decreased the expression levels of circHIPK3. Across DC samples, the expression of circHIPK3 was inversely correlated with PTEN. In AC16 cells, overexpression of circHIPK3 decreased the expression levels of PTEN. CircHIPK3 may suppress AC16 cell apoptosis induced by high glucose and inhibited the role of PTEN in cell apoptosis. Therefore, circHIPK3 may downregulate PTEN to protect cardiomyocytes from high glucose-induced cell apoptosis.