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MicroRNA-508 suppresses epithelial-mesenchymal transition, migration, and invasion of ovarian cancer cells through the MAPK1/ERK signaling pathway.
Journal of Cellular Biochemistry 2018 May 22
Ovarian cancer (OC) is the sixth most common cancer in women worldwide. Despite advances in detection and therapies, it still represents the most lethal gynecologic malignancy in the industrialized countries. Unfortunately, the molecular events that lead to the development of this highly aggressive disease remain largely unknown. The study explored the ability of microRNA-508 (miR-508) to influence proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in OC cells. We quantified the level of miR-508 cancer tissues with corresponding adjacent normal tissues collected from 84 patients with OC. Human OC cells SKOV3 and A2780 were treated with negative control (NC), miR-508 mimics, miR-508 inhibitors, and miR-508 inhibitors + a specific MAPK/ERK kinase inhibitor (PD98059) to validate the interaction between miR-508 and MAPK/ERK signaling. The miR-508 expression level was lower while MAPK1 and ERK expression levels were higher in the cancer tissues than in the adjacent normal tissues. Dual-luciferase reporter assay indicated MAPK1 as a target gene of miR-508. The miR-508 mimics reduced the expression of MAPK1, p-MAPK1, ERK, p-ERK and Vimentin, inhibited cell proliferation, migration and invasion, and increased the expression of E-cadherin, while the miR-508 inhibitors resulted in an opposed trend in OC cells. The effects of miR-508 inhibitors on OC cells were lost when the MAPK1/ERK signaling pathway was inhibited by PD98059. Collectively, our data indicate that miR-508 plays a tumor suppressor role in the development and progression of OC and may be a novel therapeutic target against OC.
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