Mir-25Promotes Cell Migration And Invasion In Esophageal Squamous Cell Carcinoma By Suppressing CDH1Expression

Esophageal cancer is the eighth most common cancer worldwide, and sixth most common cause of death from cancer. China is one of the high-risk areas. Esophageal cancer is developed from epithelia including two subtypes:esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC is the most frequent subtype of esophageal cancer in China. Resection was previously considered the mainstay of treatment for ESCC. However, there is a very poor survival that is related to invasion and metastasis. Therefore, improved morbidity and mortality of ESCC will require effective treatments targeting metastatic pathway factors. Yet the molecular mechanism of metastasis is still not completely clear.Growing evidence has indicated that microRNAs (miRNAs) as a species of small, well-conserved, non-coding single stranded RNA of about19to24nucleotides have important roles in the development of different cancers. Our previously microarray analysis demonstrated that miR-25expression was up-regulated in esophageal squamous cell carcinoma. However, the biological function of miR-25in esophageal squamous cell carcinoma is still unknown. The aim of this study was to evaluate the miR-25expression patterns and the role of miR-25in esophageal squamous cell carcinoma.In our study, we showed that the expression of miR-25was significantly increased in60ESCC tissues and five ESCC cell lines and the DNA copy number of miR-25was increased in ESCC tissues. Moreover, we found that the up-regulation of miR-25was significantly correlated with the status of lymph node metastasis and TNM (Tumor, Node and Metastasis) stage in ESCC tissues. We also assessed the level of miR-25in28cases of normal esophageal epithelia tissues (N),24dysplasia tissues (D) using qRT-PCR at the same time. Notably, the level of miR-25was significantly increased in dysplasia tissues relative to normal esophageal epithelia tissues; it was increased in advanced ESCC tumor tissues relative to dysplasia tissues. The difference was very significant. Furthermore, the over-expression of miR-25markedly promoted cell migration and invasion in vitro. On the contrary, down-regulation of miR-25inhibited the migration and invasion of cells. However, we did not observe altered cell proliferation, apoptosis and cell cycle in ESCC cells. E-cadherin (CDH1) which was a very important tumor metastasis suppressor and was down-expression in most of esophageal squamous cell carcinoma was identified as a target of miR-25by dual luciferase reporter assays. In cell lines with high miR-25expression, a low amount of CDH1protein was observed, whereas with low miR-25expression, a high amount of CDH1protein was observed. There was a significant inverse correlation between miR-25and CDH1protein levels. When CDH1was up-expressed, the ability of migration and invasion of ESCC cells induced by over-expression of miR-25was weakened.In summary, we have provided strong evidence that miR-25is frequently up-regulated in ESCC tissues. The over-expression of miR-25is along with the development of the ESCC tumorigenesis. miR-25promotes cell migration and invasion in ESCC by suppressing CDH1expression.