The effect of microRNA-9 overexpression on inhibition of melanoma cancer stem cells tumorigenicity

Abstract

Most of the studies have reported the downregulation of miR-9 in metastatic melanomas compared to primary tumors. They indicated that miR-9 negatively regulates the epithelial-to-mesenchymal transition (EMT) by inhibiting SNAIL1 expression and consequently promotes CDH1 expression. Since the process of EMT is associated to stem cell features, it could be interesting to study the effect of miR-9 on melanoma cancer stem cells. In the present study, we examined the effects of miR-9 manipulation on the stemness potential of melanoma cells. Our data demonstrated that the overexpression of miR-9 in A375 and NA8 cells significantly inhibits the ability of proliferation, self-renewal, migration, and tumorigenicity of melanoma cells which was concomitant with changes in the level of BRAF, some EMT factors, and stemness genes. Likewise, the reduction of miR-9 levels led to an increase in cell proliferation, colony and sphere formation, and the ability of cell migration and tumorigenicity. In conclusion, our results specified the role of miR-9 as a tumor suppressor miRNA to inhibit many aspects of melanoma stem cells, and therefore, it could be a potential candidate for the suppression of melanoma growth and progression.