微小RNA-23a-5p/肿瘤蛋白53诱导的核蛋白1调控胰腺癌细胞吉西他滨耐药的实验研究

目的:探讨微小RNA(microRNA，miR)调控胰腺癌吉西他滨耐药的分子作用机制。方法:反转录聚合酶链反应(qPCR)检测来自桂林医学院附属医院2015年1月至2018年12月收治的胰腺癌患者的临床标本miR-23a-5p表达水平，细胞实验检测miR-23a-5p对吉西他滨处理下肿瘤蛋白53诱导的核蛋白1(TP53...

MicroRNA-23a-5p/tumor protein p53-inducible nuclear protein 1 regulates gemcitabine resistance in pancreatic cancer cells

Objective To explore the molecular mechanism of microRNA(miRNA,miR)regulating gemcitabine resistance in pancreatic cancer.Methods The qPCR was used to detect the miR-23a-5p expression levels in clinical specimens of pancreatic cancer patients admitted from January 2015 to December 2018 in the Affiliated Hospital of Guilin Medical College.For cellular experiment,the effect of miR-23a-5p on the expression of tumor protein p53-inducible nuclear protein 1(TP53INP1)and cell proliferation and apoptosis-related factors under gemcitabine treatment was studied.The methyl thiazolyl tetrazolium(MTT)assay was used to examine the cell proliferation,and flow cytometry was done to test cell apoptosis.The luciferase reporter experiment was used to detect whether miR-23a-5p and TP53INP1 acted directly.The animal model of pancreatic cancer subcutaneous tumor formation was constructed to detect the effect of miR-23a-5p on tumor size and gemcitabine resistance in animals.All experimental data were the average of three independent experiments.Result The expression of miR-23a-5p in drug-resistant tissues increased significantly(2.267±0.334,t=4.355,P<0.01),miR-23a-5p directly targeted and regulated TP53INP1 to reduce its expression(0.423±0.095,t=5.649,P<0.01),and the proliferation activity of pancreatic cancer cells overexpressing miR-23a-5p was significantly increased(IC50=13.230)as compared with the control group(IC50=8.320,t=5.119,P<0.01).As compared with the control group(30.710±0.566)%],the proportion of apoptosis was significantly decreased(15.080±0.838)%,t=7.163,P<0.01].As compared with miR-23a-5p alone group(IC50=12.570),the proliferation level of pancreatic cancer cells treated with TP53INP1 and miR-23a-5p was significantly decreased(IC50=7.950,t=7.932,P<0.01).As compared with miR-23a-5p alone group(15.680±1.358),the apoptosis level was significantly increased(32.350±3.212,t=6.764,P<0.01)under miR-23a-5p treatment.In vivo experiments showed that knockdown of miR-23a-5p gemcitabine significantly inhibited tumor growth(169.090±25.889)cm3,t=4.351,P<0.01;(0.097±0.031)g,t=3.776,P<0.01].Conclusion MiR-23a-5p may mediate TP53INP1 regulation of pancreatic cancer cell apoptosis and gemcitabine resistance.