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 miR-183-5p 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.

Department of Urology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Hepatobiliary Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Urology,Luoshan County People's Hospital,Xinyang 464000,China;Urology Unit,La Nouvelle Polyclinique Centrale de Bujumbura,Bujumbura 378,Burundi;Department of Urology,Wuhan Red Cross Hospital,Wuhan 430015,China

[1]Qing-gang HU;Zhi YANG;Jia-wei CHEN;Gallina KAZOBINKA;Liang TIAN;Wen-cheng LI-.MiR-183-5p-PNPT1 Axis Enhances Cisplatin-induced Apoptosis in Bladder Cancer Cells)[J].当代医学科学(英文),2022(04):785-796

PNPT1,polyribonucleotide,nucleotidyltransferase,permeabilization

MiR,5p,Axis,Enhances,Cisplatin,induced,Apoptosis,Bladder,Cancer,Cells,Objective,It,has,been,reported,that,intrinsic,apoptosis,associated,progression,bladder,cancer,BC,Recent,evidence,suggests,pivotal,mediator,involved,decay,However,regulation,roles,remain,largely,unclear,Methods,upstream,miRNA,regulators,were,predicted,by,silico,analysis,levels,evaluated,real,blotting,immunohistochemistry,IHC,while,qPCR,lines,tissues,vitro,vivo,assays,performed,investigate,function,apoptotic,tumorigenic,capability,cells,Results,was,decreased,Overexpression,significantly,promoted,cisplatin,whereas,depletion,potently,alleviated,these,effects,Moreover,oncogenic,directly,targeted,UTR,reversed,suppressive,Intriguingly,modulated,not,only,but,also,Bcl2,modifying,BMF,inhibit,mitochondrial,outer,membrane,MOMP,Conclusion,Our,results,provide,new,insight,into,mechanisms,underlying,suggesting,regulatory,axis,regulates,might,represent,potential,therapeutic,avenue,treatment

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