MicroRNA-424 inhibits cell migration, invasion, and epithelial mesenchymal transition by downregulating doublecortin-like kinase 1 in ovarian clear cell carcinoma.

Abstract

Doublecortin-like kinase 1 (DCLK1) is overexpressed in many cancers and acts as a tumor stem cell marker. Here, we investigated the role of DCLK1 and microRNA-424 (miR-424) in ovarian clear cell carcinoma (OCCC), a histopathologically distinct subtype of epithelial ovarian cancer associated with poor prognosis and chemotherapy resistance. Analysis of samples from 30 OCCC patients showed that DCLK1 was upregulated and miR-424 was downregulated in tumors compared with adjacent non-tumor tissues. DCLK1 overexpression promoted OCCC cell proliferation, migration, and invasion, whereas DCLK1 knockdown reduced cell viability and invasion and induced growth arrest in vitro and in vivo. Dual-luciferase reporter assays revealed that miR-424 directly targets DCLK1 and downregulates its expression. Transfection of ES-2 cells with miR-424 mimics downregulated DCLK1 and suppressed the effects of DCLK1 overexpression on upregulating matrix metalloprotease-9 and promoting epithelial-mesenchymal transition (EMT). Taken together, these data demonstrate that miR-424 has the capacity to suppress cell invasion and EMT in OCCC by downregulating DCLK1, suggesting potential therapeutic targets and strategies for the treatment of this disease.