MicroRNA-454 inhibits tumor cell proliferation, migration and invasion by downregulating zinc finger E-box-binding homeobox 1 in gastric cancer

摘要

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-associated mortality globally. Accumulating studies have identified the involvement of microRNAs in the initiation and progression of gastric cancer. This study was aimed to investigate the expression, functional roles of microRNA-454 (miR-454) and its direct target gene in gastric cancer. According to the results, the expression level of miR-454 was demonstrated to be reduced in gastric cancer tissues and cell lines compared with corresponding distant non-tumor gastric tissues and human immortalized gastric epithelial, respectively. miR-454 mimic transfection led to inhibition of gastric cancer cells proliferation, migration and invasion in vitro. Bioinformatic analysis predicated that zinc finger E-box-binding homeobox 1 (ZEB1) is a potential target gene of miR-454. Luciferase reporter assays revealed that miR-454 directly targeted the 3'UTR of ZEB1. miR-454 overexpression significantly decreased the ZEB1 mRNA and protein expression levels. ZEB1 knockdown could mimic the tumor suppressive roles induced by miR-454 overexpression on gastric cancer cell proliferation, migration and invasion. In conclusion, the present study suggested that miR-454 under expression may be involved in gastric cancer initiation and progression, by promoting proliferation, migration and invasion by directly targeting ZEB1. miR-454/ZEB1-based targeted therapy may be a potential strategy for the treatment of gastric cancer.