MicroRNA-1 suppresses proliferation, migration and invasion by targeting Notch2 in esophageal squamous cell carcinoma

Abstract

MicroRNAs play an important role in the migration and invasion of tumors, and lower expression of microRNA-1 (miR-1) has been proven in a variety of malignant tumors, including esophageal squamous cell carcinoma (ESCC). In this study, we found that miR-1 expression levels in tumor tissues and preoperative serum from esophageal carcinoma patients were lower than those in non-tumorous tissues and healthy volunteers. miR-1 expression in tissues and plasma was closely related to invasion, lymph node metastasis and TNM staging. Additionally, miR-1 expression levels in tissues and plasma were positively correlated. miR-1 inhibited cell proliferation, migration and invasion. Overexpression of miR-1 in ESCC cells reduced Notch2 protein but not mRNA levels, whereas suppression of miR-1 led to an increase in Notch2 protein but not mRNA levels. A dual-luciferase experiment validated that Notch2 was a direct target of miR-1. Introducing Notch2 mRNA into cells over-expressing miR-1 partially abrogated the effects of miR-1 on migration and invasion. Further studies verified that miR-1 regulates EMT signalling pathways directly through Notch2. Therefore, these results confirm that, as a tumor suppressor gene, miR-1 may be a potential tumor marker for the early diagnosis of ESCC and a new drug target.