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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(TP53INP1)及细胞增殖和凋亡相关因子表达的影响，噻唑蓝(MTT)检测细胞增殖，流式细胞术检测细胞凋亡情况。荧光素酶报告实验检测miR-23a-5p和TP53INP1是否直接作用。构建胰腺癌皮下成瘤小鼠模型，检测动物体内miR-23a-5p瘤体大小和吉西他滨耐药性的影响，组间比较采用多重比较检验或n t检验。n 结果:耐药组织中miR-23a-5p的表达量显著高于不耐药组(2.267±0.334，n t＝4.355，n P<0.01)，miR-23a-5p直接靶向调控TP53INP1降低其表达(0.423±0.095，n t＝5.649，n P<0.01)，miR-23a-5p过表达组(ICn 50＝13.23)胰腺癌细胞增殖活性显著高于对照组(ICn 50＝8.32，n t＝5.119，n P<0.01)，细胞凋亡比例[(15.080±0.838)%]显著低于对照组[(30.710±0.566)%，n t＝7.163，n P<0.01]，TP53INP1和miR-23a-5p共处理组(ICn 50＝7.932)胰腺癌细胞增殖水平显著低于miR-23a-5p单独处理组(ICn 50＝12.570，n t＝12.57，n P<0.01)，凋亡水平[(32.350±3.212)%]显著高于miR-23a-5p单独处理组[(15.680±1.358)%，n t＝6.764，n P<0.01]，动物实验结果表明敲低miR-23a-5p吉西他滨处理后显著抑制肿瘤生长[(169.090±25.889) cmn 3，n t＝4.351，n P<0.01；(0.097±0.031) g，n t＝3.776，n P<0.01]，差异均有统计学意义。n 结论:miR-23a-5p介导TP53INP1调控胰腺癌细胞凋亡和吉西他滨耐药。“,”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, n t=4.355, n P<0.01), miR-23a-5p directly targeted and regulated TP53INP1 to reduce its expression (0.423±0.095,n t=5.649, n P<0.01), and the proliferation activity of pancreatic cancer cells overexpressing miR-23a-5p was significantly increased (ICn 50=13.230) as compared with the control group (ICn 50=8.320, n t=5.119, n P<0.01). As compared with the control group [(30.710±0.566)%], the proportion of apoptosis was significantly decreased [(15.080±0.838)%,n t=7.163, n P<0.01]. As compared with miR-23a-5p alone group (ICn 50=12.570), the proliferation level of pancreatic cancer cells treated with TP53INP1 and miR-23a-5p was significantly decreased (ICn 50=7.950, n t=7.932, n 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,n t=6.764, n P<0.01) under miR-23a-5p treatment.n In vivo experiments showed that knockdown of miR-23a-5p gemcitabine significantly inhibited tumor growth [(169.090±25.889) cmn 3, n t=4.351, n P<0.01; (0.097±0.031) g,n t=3.776, n P<0.01].n Conclusion:MiR-23a-5p may mediate TP53INP1 regulation of pancreatic cancer cell apoptosis and gemcitabine resistance.