FOXC2通过调节SNCA促进鼻咽癌化疗抗性的研究  

FOXC2 Promotes Chemoresistance in Nasopharyngeal Carcinomas via Regulating SNCA

作　　者：蔡格 袁源[1] 周志姣[1] CAI Ge;YUAN Yuan;ZHOU Zhijiao(Department of Pathology,The Third Xiangya Hospital of Central South University,Changsha,Hunan,410013,China)

机构地区：[1]中南大学湘雅三医院病理科,湖南长沙410013

出　　处：《肿瘤药学》2020年第5期540-544,共5页Anti-Tumor Pharmacy

基　　金：国家自然科学基金(81602647);湖南省自然科学基金(2020JJ4867,2017JJ3472)。

摘　　要：目的筛选鼻咽癌紫杉醇化疗抗性细胞死亡相关基因,并探讨筛选出的基因SNCA与FOXC2的相关性。方法通过Cell Death PCR array筛选鼻咽癌化疗敏感细胞(CNE2)和化疗抗性细胞(CNE2/t)之间的差异表达基因。采用Realtime PCR和Western blotting检测CNE2和CNE2/t中SNCA的表达差异;采用Real-time PCR检测FOXC2干扰的CNE2/t细胞及其阴性对照细胞中SNCA的表达变化;运用JASPAR数据库预测FOXC2对SNCA的靶向调控作用。结果通过Cell Death PCR array筛选出了CNE2和CNE2/t之间的差异表达基因SNCA。与CNE2细胞相比,CNE2/t细胞中SNCA的mRNA及蛋白表达水平均显著上调(P<0.01)。与阴性对照细胞相比,FOXC2干扰的CNE2/t细胞中SNCA的mRNA表达水平显著下调(P<0.01)。JASPAR数据库预测结果显示,SNCA启动子区中存在FOXC2的结合位点。结论SNCA表达上调与鼻咽癌紫杉醇化疗抗性密切相关,FOXC2可通过调节SNCA促进鼻咽癌的化疗抗性。Objective To screen cell death related genes in paclitaxel-resistant nasopharyngeal carcinoma cell,and to study the relationship between SNCA and FOXC2 in chemo-resistant nasopharyngeal carcinoma cells.Methods The differentially expressed genes involved in cell death were examined through cell death PCR array in paclitaxel-sensitive CNE2 and paclitaxel-resistant CNE2/t cells.SNCA expression in CNE2 and CNE2/t was examined by real-time PCR and Western blotting analysis.SNCA expression in FOXC2-knockdown stable CNE2/t cells was examined by real-time PCR analysis.The JASPAR database was used to predict the targeted regulation effect of FOXC2 on SNCA.Results The differentially expressed genes involved in cell death were screened.Compared with the control CNE2 cells,SNCA expression in CNE2/t cells was increased(P<0.01).SNCA expression was significantly down-regulated in FOXC2-knockdown stable cells,compared with the control CNE2/t cells(P<0.01).The JASPAR database prediction results showed that there was FOXC2 binding site in SNCA promoter region.Conclusion Up-regulation of SNCA expression was closely associated with paclitaxel-resistance in NPC.FOXC2 promoted chemoresistance of nasopharyngeal carcinomas via regulating SNCA.

关 键 词：SNCA 化疗抗性 鼻咽癌 

分 类 号：R739.6[医药卫生—肿瘤]