微小RNA-126通过靶向细胞粘附分子1调控胃癌的迁移和侵袭。
MicroRNA-126 regulates migration and invasion of gastric cancer by targeting CADM1.
作者信息
Yang Zhen, Wang Ruoming, Zhang Tengteng, Dong Xinhua
机构信息
Department of Gastrointestinal Surgery, First Affiliated Hospital of Zhengzhou University China.
Department of General Surgery, First Renmin Hospital of Shangqiu Henan Province, China.
出版信息
Int J Clin Exp Pathol. 2015 Aug 1;8(8):8869-80. eCollection 2015.
OBJECTIVE
The aberrant expression of microRNAs has been demonstrated to play a crucial role in the initiation and progression of gastric cancer (GC). We here aimed to investigate the mechanism of microRNAs in the regulation of GC pathogenesis.
METHODS
Transwell chambers (8-μM pore size; Costar) were used in the in vitro migration and in vision assay. Dual luciferase reporter gene construct and dual luciferase reporter assay to identify the target of miR-126. CADM1 expression was evaluated by immunohistochemical staining. The clinical manifestations, treatments and survival were collected for statistical analysis.
RESULTS
Inhibition of miR-126 effectively reduced migration and invasion of gastric cancer cell lines. Bioinformatics and luciferase reporter assay revealed that miR-126 specifically targeted the 3'UTR of cell adhesion molecule 1 (CADM1) and regulated its expression. Down-regulation of CADM1 enhanced migration and invasion of GC cell lines. Furthermore, in tumor tissues obtained from gastric cancer patients, the expression of miR-126 was negatively correlated with CADM1 and the high expression of miR-126 combined with low expression of CADM1 might serve as a risk factor for stage1 gastric cancer patients.
CONCLUSIONS
Our study showed that miR-126, by down-regulation CADM1, enhances migration and invasion in GC cells.
目的
微小RNA的异常表达已被证明在胃癌（GC）的发生和发展中起关键作用。我们旨在研究微小RNA在调控胃癌发病机制中的作用机制。
方法
使用Transwell小室（孔径8μm；Costar）进行体外迁移和体内实验。采用双荧光素酶报告基因构建体和双荧光素酶报告基因检测来鉴定miR-126的靶标。通过免疫组织化学染色评估细胞粘附分子1（CADM1）的表达。收集临床表现、治疗方法和生存率进行统计分析。
结果
抑制miR-126可有效降低胃癌细胞系的迁移和侵袭能力。生物信息学和荧光素酶报告基因检测显示，miR-126特异性靶向细胞粘附分子1（CADM1）的3'非翻译区并调节其表达。CADM1表达下调增强了胃癌细胞系的迁移和侵袭能力。此外，在胃癌患者的肿瘤组织中，miR-126的表达与CADM1呈负相关，miR-126高表达与CADM1低表达可能是Ⅰ期胃癌患者的危险因素。
结论
我们的研究表明，miR-126通过下调CADM1增强胃癌细胞的迁移和侵袭能力。
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