摘要目的 观察微小RNA-126(miR-126)在食管鳞癌组织中的表达及其可能调控的靶基因.方法 采用实时定量反转录聚合酶链反应(RT-qPCR)法,检测75例患者食管鳞癌组织和其匹配的癌旁组织中miR-126的表达水平,应用软件预测miR-126的靶基因,免疫组织化学法分析靶蛋白在癌组织中的表达,在食管鳞癌细胞中提高或降低miR-126表达水平,验证其对靶基因的调控作用.结果 对75组配对标本分析,癌组织中miR-126的相对表达量为0.28±0.32,癌旁组织为0.45±0.47,差异有统计学意义(P＜0.01);miR-126低表达与食管鳞癌分化程度、淋巴结转移、肿瘤浸润深度和临床分期相关(P＜0.05);胰岛素受体底物-1(IRS-1)在食管鳞癌组织中过表达,与肿瘤分化程度有关(P＜0.01);上调食管鳞癌细胞Eca9706、Eca109、TE-1中miR-126的表达会导致IRS-1蛋白的表达量(0.785±0.337、1.873±0.684、1.938±1.081)较空白组(1.188±0.336、2.756±1.097、3.028±0.789)下降(P＜0.01),下调食管鳞癌细胞中miR-126的表达会导致IRS-1蛋白的表达量(2.543±0.610、5.182±1.897、5.940±0.997)相对升高(P＜0.01).结论 食管鳞癌组织中miR-126表达水平下降,IRS-1蛋白的表达受miR-126的负调控,IRS-1可能是miR-126在食管鳞癌中发挥抑癌基因功能的靶基因之一.

abstractsObjective To investigated microRNA (miR)-126 expression and its potential targets in esophageal squamous cell carcinoma (ESCC).Methods The expression level of miR-126 was detected in cancerous and paired paracancerous tissues from 75 patients with ESCC,association between miR-126 level and clinicopathologic characteristics were analysised.Target analysis of miR-126 was predicted using online tools.The effect of miR-126 expression on target proteins was assessed through up/down miR-126 level in ESCC cell lines.Results The relative expression of miR-126 in ESCC tissues was 0.28 ± 0.32 and 0.45 ± 0.47 in normal tissues (P ＜ 0.01).Low level of miR-126 was associated with tumor differentiation,lymph nodes metastasis,tumor in-depth,and TNM stages (P ＜ O.05).Insulin receptor substrate-1 (IRS-1) was over-expressed and associated with cell differentiation (P ＜0.01).In ESCC cell line Eca9706,Eca109 and TE-1,miR-126 mimics down-regulated the expression of IRS-1 protein (0.785 ± 0.337,1.873 ± 0.684,1.938 ± 1.081) compared with non-treated control (1.188 ± 0.336,2.756 ± 1.097,3.028 ± 0.789,P ＜ 0.01),whereas miR-126 inhibitors lead to the opposite results (2.543±0.610,5.182±1.897,5.940±0.997,P＜0.01).Conclusion This study revealed that miR-126 is low-expressed in ESCC and acts as a tumor suppressor in the carcinogenesis of ESCC.IRS-1 was downstream targets of miR-126 in ESCC.