miR-106a在食管鳞癌中的表达及对耐药基因的调控作用  

Expression of miR-106a in esophageal squamous cell carcinoma and its role for the regulation of drug-resistant genes

作　　者：吕望[1] 袁小帅[1] 汪路明[1] 王志田[1] 韩威力[1] 

机构地区：[1]浙江大学医学院附属第一医院胸外科,浙江杭州310003

出　　处：《海南医学院学报》2015年第5期582-587,共6页Journal of Hainan Medical University

基　　金：浙江省自然科学基金(Y2090470)~~

摘　　要：目的:探讨MicroRNA-106a(miR-106a)在食管鳞状细胞癌(ESCC)中的表达情况及对耐药相关基因三磷酸腺苷结合蛋白G亚族成员2(ABCG2)、信号转导与转录激活因子3(STAT3)的调控作用。方法:收集本院胸外科行手术切除的ESCC组织及对应癌旁组织共60例,运用qRT-PCR检测miR-106a在ESCC组织及癌旁组织中的表达水平,统计分析miR-106a表达水平与患者临床病理资料间的相关性;免疫组化检测不同miR-106a含量的食管鳞癌组织中miR-106下游潜在靶点ABCG2及STAT3蛋白的表达水平,统计分析ABCG2及STAT3蛋白与miR-106a表达间的相关性;采用人工合成的miR-106a模拟物(miR-106amimics)转染人食管鳞癌TE-1细胞,分别采用qRT-PCR及WesternBlot检测转染后ABCG2及STAT3mRNA及蛋白的表达变化。结果:miR-106a在ESCC组织中表达水平明显低于对应癌旁组织,差异具有统计学意义(P<0.05);miR-106a低表达与肿瘤体积增大(>5cm)、淋巴结转移及高TNM分期(Ⅲ+IV期)明显相关(P<0.05);在食管鳞癌组织中miR-106a与ABCG2及STAT3的表达呈负相关关系(P<0.05),miR-106a转染人食管鳞癌TE-1细胞可明显降低细胞内ABCG2及STAT3mRNA及蛋白的表达水平(P<0.05)。结论:miR-106a在食管鳞癌组织中表达下调并与肿瘤恶性临床病理特征有关,miR-106a可能通过下调ABCG2及STAT3的表达来调控食管鳞癌的耐药表型。Objective： To investigate the expression of MicroRNA-106a in esophageal squamous cell carcinoma （ESCC） and its role for the regulation of drug-resistant genes, ABCG2 and STAT3. Methods＇ qRT-PCR was used to detect the relative expression of miR-106a in 60 paired ESCC and matched tumor adjacent tissues. The relationship between the miR-106a expres- sion and clinical features were used Pearson ehi-square test. The expressions of ABCG2 and STAT3 were measured by immu nohistochemistry （IHC）, Spearman correlation analysis was used to analyze the relationship between miR-106a and ABCG2 and STAT3. We then transfected the miR-106a mimics into TE-1 ceils, then the Western-Blot was used to detect tb.e expres- sion of ABCG2 and STAT3, which are considered as the potential targets of miR-106a. Results： The relative expressions of miR-106a was significantly down-regulated in ESCC tissues compared to those of the matched tumor-adjacent tissues （P〈0.05）. Low expression of miR-106a was significantly associated with large tumor size （〉5 cm）, lymphatic metastasis and ad- vanced TNM stage （ Ⅲ ＋ Ⅳ）. The expressions of ABCG2 and STAT3 in lower miR-106a level group were both up-regulation than in higher miR-106a level group （P%0.05）. Both the mRNA and protein expression in TE-1 cells were down-regulated af- ter transfection of miR-106a mimics. Conclusion： Low expression of miR-106a is related to the malignant clinicopathological features in ESCC tissues, and miR-106a may be through down-regulating ABCG2 and STAT3 to suppress drug resistance of ESCC.

关 键 词：MicroRNA-106a 食管鳞癌 三磷酸腺苷结合蛋白G亚族成员2(ABCG2) 信号转导与转录激活因子3(STAT3) 

分 类 号：R735.1[医药卫生—肿瘤]