MicroRNA-455 is downregulated in gastric cancer and inhibits cell proliferation, migration and invasion via targeting insulin-like growth factor 1 receptor

Abstract

Gastric cancer is the fourth most common and the second leading cause of cancer mortality worldwide. The dysregulation of microRNAs has been demonstrated to be significant in gastric cancer carcinogenesis and progression due to changes in expression of their target genes. In the current study, microRNA-455 (miR-455) was identified to be significantly downregulated in gastric cancer tissue samples and cell lines. A low expression level of miR-455 was correlated with the clinical stage, lymph node metastasis and tumor invasion in gastric cancer. Restoration of miR-455 expression inhibited cell proliferation, migration and invasion of gastric cancer cells in vitro. Bioinformatic analysis and luciferase reporter assay revealed that miR-455 directly targeted the 3'-untranslated region of insulin-like growth factor 1 receptor (IGF-1R). In addition, the IGF-1R mRNA expression level was increased in gastric cancer tissue samples and was inversely correlated with miR-455 expression levels. Restoration of miR-455 downregulated IGF-1R mRNA and protein expression levels in gastric cancer cells. Furthermore, silencing of IGF-1R significantly inhibited gastric cancer cell proliferation, migration and invasion, which was similar to the functions induced by miR-455 overexpression. Thus, these results indicate that miR-455 is involved in gastric cancer progression by directly targeting IGF-1R and may serve as a novel therapeutic target for the treatment of gastric cancer.