MicroRNA-455 inhibits cell proliferation and invasion of epithelial ovarian cancer by directly targeting Notch1

Ovarian cancer (OC) is the fifth leading cause of cancer-associated mortality among women in developed countries. Numerous microRNAs are aberrantly expressed in epithelial (E) OC, and are involved in EOC formation and progression. As such, microRNAs may be investigated as diagnostic and prognostic molecular biomarkers, and therapeutic targets for patients with EOC. For instance, microRNA-455 (miR-455) is abnormally expressed in various types of human cancer. However, details on the expression level, biological roles and underlying mechanism of miR-455 in EOC remain unclear. In the present study, the expression of miR-455 in EOC was detected, and its association with clinical characteristics was analysed. The functional roles and underlying mechanisms of miR-455 in EOC were also investigated. The results revealed that miR-455 expression in EOC tissues and cell lines was significantly downregulated. Furthermore, miR-455 downregulation was correlated with tumor size, International Federation of Gynecology and Obstetrics stage and lymph node metastasis of patients with EOC. Restoration of miR-455 expression efficiently inhibited cell proliferation and invasion in vitro. Notch1 was identified as a direct target of miR-455 in EOC. The mRNA and protein expression levels of Notch1 were higher in EOC tissues compared with in normal ovarian epithelial tissues. Spearman's correlation analysis indicated that miR-455 expression was negatively correlated with the mRNA level of Notch1 in EOC tissues. Notch1 overexpression was able to restore the EOC cell proliferation and invasion abilities suppressed by miR-455. The present study provided evidence that the dysregulation of the miR-455/Notch1 signalling pathway may be essential for EOC occurrence and development. In addition, the results confirmed the tumor-suppressive roles of miR-455 in modulating EOC proliferation and invasion through regulation of Notch1 expression. Thus, miR-455 may be a novel miRNA-based therapeutic target to treat patients with EOC.