Enhanced Expression of miR-425 Promotes Esophageal Squamous Cell Carcinoma Tumorigenesis by Targeting SMAD2.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers in the world. Currently, clinical therapy of ESCC remains limited and the five-year survival rate is poor. The function of miR-425 has been reported in multiple human cancers. However, the tumorigenic role and clinical significance of miR-425 in ESCC remains unclear. We found that enhanced expression of miR-425 in ESCC cell lines not only promoted cell proliferation and colony formation, but also increased cellular metastasis. Furthermore, we revealed the mechanism that miR-425 inhibited the expression of SMAD2 by targeting the second binding site in the 3'-untranslated region (3'-UTR) in ESCC. This mode of action influenced not only SMAD2 mRNA expression but also protein expression. In addition, we detected the expression of miR-425 in ESCC tissues and plasma. Moreover, we analyzed the relationship between miR-425 expression and SMAD2 mRNA expression. We found that miR-425 was overexpressed in ESCC tissues and the plasma relative to adjacent normal tissues and plasma of healthy individuals. Furthermore, there was a negative correlation between miR-425 expression and SMAD2. Taken together, our results show that miR-425 functions as an oncogene by targeting the 3'-UTR of SMAD2 and indicate the potential utility of plasma miR-425 as a novel biomarker for ESCC diagnosis.