Upregulated microRNA-25 mediates the migration of melanoma cells by targeting DKK3 through the WNT/β-catenin pathway

Abstract

Previous research indicates that microRNA-25 (miR-25) regulates carcinogenesis and the progression of various cancers, but the role of miR-25 in melanoma remains unclear. We observed that miR-25 was significantly upregulated in melanoma cell lines and tissue samples. Downregulation of miR-25 markedly suppressed invasion and proliferation of melanoma cells in vitro; however, overexpression of miR-25 markedly increased melanoma cell invasion and proliferation. Moreover, we observed Dickkopf-related protein 3 (DKK3) as a direct target of miR-25 in vitro. Upregulation of DKK3 partially attenuated the oncogenic effect of miR-25 on melanoma cells. Ectopic expression of miR-25 in melanoma cells induced β-catenin accumulation in nuclear and inhibited TCF4 (T cell factor 4) activity, as well as the expression of c-Myc and Cyclin D1. In a nude xenograft model, miR-25 upregulation significantly increased A375 melanoma growth. In summary, miR-25 is upregulated in melanoma and promotes melanoma cell proliferation and invasion, partially by targeting DKK3. These results were indicated that miR-25 may serve as a potential target for the treatment of melanoma in the future.