miR-26a通过调控Wnt/β-catenin信号通路抑制食管癌发生发展

miR-26a inhibits the occurrence and development of esophageal cancer by regulating Wnt/β-catenin signaling pathway

目的探讨miR-26a在裸鼠体内对食管癌发生发展以及调控Wnt/β-catenin信号通路的影响。方法在45对手术切除并经病理检查证实食管鳞癌组织和正常癌旁组织配对样本中,用RT-PCR检测miR-26a的表达,通过慢病毒干扰技术在食管癌细胞株中干扰miR-26a和过表达miR-26a,并将在裸鼠荷瘤实验中观察肿瘤细胞的成瘤情况。采用免疫组织化学技术检测各组裸鼠肿瘤组织中Wnt/β-catenin信号通路相关蛋白(细胞周期蛋白D1、c-myc和β-catenin)的表达。结果相对于食管癌旁组织,miR-26a在食管癌组织中的表达显著降低;miR-26a对食管鳞癌细胞凋亡无明显影响,但能抑制裸鼠瘤体的生长,过表达miR-26a的裸鼠瘤体显著小于对照组,干扰miR-26a表达的裸鼠瘤体显著大于对照组。免疫组织化学染色显示,在食管鳞癌组织中,过表达miR-26a使细胞周期蛋白1、c-myc和β-catenin水平显著下调,抑制miR-26a表达则使这3种蛋白水平显著上调。结论miR-26a抑制食管癌发生、发展,miR-26a可能通过抑制Wnt/β-catenin信号转导抑制食管癌的进展。

Objective To investigate the effect of miR-26a on the occurrence and development of esophageal cancer and the regulation of Wnt/β-catenin signaling pathway in nude mice.Methods In 45 pairs of samples collected from esophageal squamous cell carcinoma(ESCC)tissue and normal adjacent tissue,RT-PCR was used to detect the expression of miR-26a.Interference of miR-26a expression(miR-26a interference group)and overexpression of miR-26a(miR-26a overexpression group)were performed with lentiviral transfection,and tumor cells were observed for tumor-bearing in nude mice.Immunohistochemical methods were used to detect the expression of Wnt/β-catenin signaling pathway related proteins(cyclinD1,c-myc andβ-catenin)and the expression of miR-26a in tumor tissues of nude mice.Results Compared with adjacent tissues of esophageal cancer,the expression of miR-26a in esophageal cancer tissues was significantly decreased.miR-26a has no observable effect on the apoptosis of ESCC cells.miR-26a can inhibit the growth of tumor volume in nude mice.The tumor volume of the overexpression group was significantly smaller than that of the control group.The tumor volume in the miR-26a interference group was significantly larger than that in the control group.In the miR-26a overexpression group,the expression levels of cyclin D1 protein was down-regulated,and the expression of c-myc andβ-catenin protein was also down-regulated;whilst in the miR-26a interference group,the expression level of cyclin D1,c-myc andβ-catenin were up-regulated.Conclusion miR-26a inhibits the occurrence and development of esophageal cancer.The anti-cancer effect of miR-26a in esophageal cancer may be related to the regulation of Wnt/β-catenin signaling pathway.