MiR-877-3p Induces Apoptosis by Targeting BCL2 in Tubular Epithelial Cells

Abstract

Background: Apoptosis of renal tubular epithelial cells plays an important role in the progression of diabetic kidney disease(DKD). Our previous study found that miR-877-3p of urinary exosomes significantly increased in patients with DKD, but its mechanism of action in DKD remains unclear. Here, we found that miR-877-3p significantly aggravated the progression of diabetic kidney disease. miR-877-3p was found to significantly increase tubular epithelial cell apoptosis and appeared to act by down-regulating the anti-apoptotic gene BCL2 in human proximal tubule cell line(HK-2 cell). Bioinformatics software and luciferase reporter gene analysis showed that miR-877-3p promotes apoptosis and aggravates the progression of DKD through targeting BCL2 3’UTR region in HK-2 cells. Methods: miR-877-3p and BCL2 were detected in HFD/STZ-induced mice upon their sacrifice at 6 and 12 w. In vitro studies, we incubated HK-2 cells under high-glucose (HG) to mimic DKD.Then,BCL2 expression was detected in HK-2 cells with overexpression of miR-877-3p. BCL2, Bax and cleaved caspase3 gene and protein expression levels were determined by RT-qPCR and western blotting, respectively.The direct relationship between miR-877-3p and BCL2 was explored via luciferase reporter assay. Results: miR-877-3p expression was more significantly increased in the renal cortices of diabetes mellitus (DM) mice at 12 w after treatment compared to the renal cortices of 6W.In contrast, BCL2 expression was significantly decreased in DM mice compared to control mice only at 12 w after treatment.We also found that miR-877-3p was increased in HG treated HK-2 cells.Overexpression of miR-877-3p in HK-2 cells downregulate the expression of BCL2. Conclusions: miR-877-3p promotes DKD progression through targeting BCL2. Disclosure M. Zou: None. M. Xue: None. F. Hu: None. Y. Jia: None. Y. Yang: None. Y. Xue: None.