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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。
Abstract:Objective:To investigate the expression of MicroRNA-106 ain 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-106 ain 60paired ESCC and matched tumor adjacent tissues.The relationship between the miR-106 aexpression and clinical features were used Pearson chi-square test.The expressions of ABCG2 and STAT3were measured by immunohistochemistry(IHC),Spearman correlation analysis was used to analyze the relationship between miR-106 aand ABCG2and STAT3.We then transfected the miR-106 amimics into TE-1cells,then the Western-Blot was used to detect the expression of ABCG2 and STAT3,which are considered as the potential targets of miR-106 a.Results:The relative expressions of miR-106 awas significantly down-regulated in ESCC tissues compared to those of the matched tumor-adjacent tissues(P<0.05).Low expression of miR-106 awas significantly associated with large tumor size(>5cm),lymphatic metastasis and advanced TNM stage(Ⅲ + Ⅳ).The expressions of ABCG2 and STAT3in lower miR-106 alevel group were both up-regulation than in higher miR-106 alevel group(P<0.05).Both the mRNA and protein expression in TE-1cells were down-regulated after transfection of miR-106 amimics.Conclusion:Low expression of miR-106 ais related to the malignant clinicopathological features in ESCC tissues,and miR-106 amay be through down-regulating ABCG2 and STAT3to suppress drug resistance of ESCC.
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基本信息:
DOI:10.13210/j.cnki.jhmu.20150108.016
中图分类号:R735.1
引用信息:
[1]吕望,袁小帅,汪路明,等.miR-106a在食管鳞癌中的表达及对耐药基因的调控作用[J].海南医学院学报,2015,21(05):582-587.DOI:10.13210/j.cnki.jhmu.20150108.016.
基金信息:
浙江省自然科学基金(Y2090470)~~
2015-01-08
2015-01-08
2015-01-08