miR-33-5p靶向调控JNK1/c-Jun通路降低口腔鳞状细胞癌多重耐药性  

MiR-33-5p targets the JNK1/c-Jun pathway to reduce the multidrug resistance of oral squamous cell carcinoma

作　　者：韩永洁[1] 王兴国 邓璐 杜蔚蔚 Han Yongjie;Wang Xingguo;Deng Lu(Dept of Maxillofacial Surgery,Qinghai Provincial People’s Hospital,Xining 810007;Dept of Oncology,Qinghai Provincial People’s Hospital,Xining 810007)

机构地区：[1]青海省人民医院颌面外科,西宁810007 [2]青海省人民医院肿瘤内科,西宁810007

出　　处：《安徽医科大学学报》2021年第2期227-232,共6页Acta Universitatis Medicinalis Anhui

基　　金：青海省卫生健康委员会课题(编号:2017-wjzdx-08)。

摘　　要：目的探讨miR-33-5p调控c-Jun氨基末端激酶1(JNK1)通路对人口腔鳞状细胞癌多重耐药性的影响。方法 CAL-27细胞分为CAL-27组、CAL-27/CBP组、CAL-27/CBP+scramble inhibitor组、CAL-27/CBP+miR-33-5p inhibitor组,卡铂(CBP)诱导耐药细胞株,根据组别转染scramble inhibitor或miR-33-5p inhibitor,MTT检测细胞的多重耐药性,RT-PCR检测miR-33-5p的表达,荧光素酶报告实验检测miR-33-5p和JNK1靶向作用,Western blot检测JNK1/c-Jun通路的激活以及MDR1的表达,流式细胞术检测Rh123聚集结果。结果与CAL-27组比较,CAL-27/CBP的多重耐药性提高(P<0.01),miR-33-5p表达水平升高(P<0.01),JNK1/c-Jun通路活化水平降低(P<0.01),Rh123阳性细胞百分比降低(P<0.01),MDR1蛋白水平升高(P<0.01),同时荧光素酶报告实验结果显示miR-33-5p靶向作用于JNK1;与CAL-27/CBP组比较,CAL-27/CBP+miR-33-5p inhibitor组细胞的多重耐药性降低(P<0.05),miR-33-5p表达水平降低(P<0.01),JNK1/c-Jun通路活化水平升高(P<0.01),Rh123阳性细胞百分比升高(P<0.01),MDR1蛋白水平降低(P<0.01)。结论 miR-33-5p通过靶向调控JNK1/c-Jun通路降低CAL-27/CBP耐药细胞株的多重耐药性。Objective To investigate the effect of miR-33-5 p on the regulation of c-Jun amino terminal kinase 1(JNK1) on the multi-drug resistance of human oral squamous cell carcinoma.Methods CAL-27 cells were divided into CAL-27 group,CAL-27/CBP group,CAL-27/CBP+ scramble inhibitor group,CAL-27/CBP+ miR-33-5 p inhibitor group,carboplatin(CBP) induced drug resistance Cell line,according to the group transfected with scramble inhibitor or miR-33-5 p inhibitor.MTT detected the multi-drug resistance of cells,RT-PCR detected the expression of miR-33-5 p,luciferase report test detected miR-33-5 p With JNK1 targeting,Western blot was used to detect the activation of the JNK1/c-Jun pathway and the expression of MDR1,and flow cytometry was used to detect the results of Rh123 aggregation.Results Compared with CAL-27 group,the multi-drug resistance of CAL-27/CBP increased(P<0.01),the expression level of miR-33-5 p increased(P<0.01),and the activation level of JNK1/c-Jun pathway decreased(P<0.01),the percentage of Rh123 positive cells decreased(P<0.01),the level of MDR1 protein increased(P<0.01),and the luciferase reported experimental results showed that miR-33-5 p targeted JNK1;compared with the CAL-27/CBP group,the multi-drug resistance of cells in the CAL-27/CBP+miR-33-5 p inhibitor group reduced(P<0.05),the expression level of miR-33-5 p reduced(P<0.01),The activation level of JNK1/c-Jun pathway increased(P<0.01),the percentage of Rh123 positive cells increased(P<0.01),and the level of MDR1 protein decreased(P<0.01).Conclusion MiR-33-5 p reduces the multi-drug resistance of CAL-27/CBP drug-resistant cell lines through targeted regulation of JNK1/c-Jun pathway.

关 键 词：口腔鳞状细胞癌 多重耐药性 JNK1 miR-33-5p 

分 类 号：R739.8[医药卫生—肿瘤]