MiR-183-5p-PNPT1 Axis Enhances Cisplatin-induced Apoptosis in Bladder Cancer Cells

Objective:It has been reported that intrinsic apoptosis is associated with the progression of bladder cancer(BC).Recent evidence suggests that polyribonucleotide nucleotidyltransferase 1(PNPT1)is a pivotal mediator involved in RNA decay and cell apoptosis.However,the regulation and roles of PNPT1 in bladder cancer remain largely unclear.Methods:The upstream miRNA regulators were predicted by in silico analysis.The expression levels of PNPT1 were evaluated by real-time PCR,Western blotting,and immunohistochemistry(IHC),while miR-183-5p levels were evaluated by qPCR in BC cell lines and tissues.In vitro and in vivo assays were performed to investigate the function of miR-183-5p and PNPT1 in apoptotic RNA decay and the tumorigenic capability of bladder cancer cells.Results:PNPT1 expression was decreased in BC tissues and cell lines.Overexpression of PNPT1 significantly promoted cisplatin-induced intrinsic apoptosis of BC cells,whereas depletion of PNPT1 potently alleviated these effects.Moreover,oncogenic miR183-5p directly targeted the 3′UTR of PNPT1 and reversed the tumor suppressive role of PNPT1.Intriguingly,miR-183-5p modulated not only PNPT1 but also Bcl2 modifying factor(BMF)to inhibit the mitochondrial outer membrane permeabilization(MOMP)in BC cells.Conclusion:Our results provide new insight into the mechanisms underlying intrinsic apoptosis in BC,suggesting that the miR-183-5p-PNPT1 regulatory axis regulates the apoptosis of BC cells and might represent a potential therapeutic avenue for the treatment of BC.