MicroRNA-320 targets mitogen-activated protein kinase 1 to inhibit cell proliferation and invasion in epithelial ovarian cancer

摘要

Ovarian cancer is the second most frequently occurring cancer and the most fatal gynecological malignancy of all gynecological cancers worldwide. MicroRNAs (miR) have been reported to be downregulated or upregulated in a variety of human malignancies, and involved in the formation and progression of the majority of human cancers, including epithelial ovarian cancer (EOC). miR-320 has been identified as a tumor suppressor in multiple human cancers. However, the expression levels, biological role and underlying mechanisms of miR-320 in EOC remain to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-320 expression in EOC tissues and cell lines. Following transfection with miR-320 mimics, Cell Counting Kit 8 and cell invasion assays were utilized to investigate the effects of miR-320 on EOC cell proliferation and invasion. Bioinformatic analysis, luciferase reporter assay, RT-qPCR and western blotting were used to explore the underlying mechanism of how miR-320 affects cell proliferation and invasion in EOC. Mitogen-activated protein kinase (MAPK) 1 expression and its association with the miR-320 expression level was examined in EOC tissues. The role of MAPK1 in EOC cells was additionally evaluated by using a loss-of-function assay. The results demonstrated that miR-320 was markedly downregulated in EOC tissues and cell lines. A decreased miR-320 expression was significantly correlated with the Federation of Gynecology and Obstetrics stage and lymph node metastasis of EOC patients. Additionally, reintroduction of miR-320 expression suppressed cell proliferation and invasion in EOC. Furthermore, it was verified that MAPK1 is a direct target gene of miR-320 in EOC. MAPK1 expression was markedly upregulated in EOC tissues and inversely correlated with miR-320 expression. Furthermore, silencing of MAPK1 by RNA interference inhibited cell proliferation and invasion of EOC cells. Overall, the present study demonstrated that miR-320 may act as a useful diagnostic and therapeutic target in the treatment of EOC.