More and more evidence suggests that
microRNA (
miRNA) and RNA editing play key roles in the development and progression of
tumor. However, the influence of
miRNA-mediated RNA editing on tumor stem cells remains unclear. In this study, the results demonstrated that miR-17, which was downregulated in
melanoma stem cells, acted as a
tumor inhibitor by suppressing the stemness of
melanoma stem cells and promoting cell differentiation. MiR-17 targeted ADAR2 (
adenosine deaminase acting on
RNA 2), a gene encoding an editing
enzyme required for the maintenance of
melanoma stem cell stemness. In
melanoma stem cells, ADAR2 was responsible for DOCK2
mRNA editing, which was able to increase the stability of DOCK2
mRNA. The in vitro and in vivo data demonstrated that DOCK2
mRNA editing upregulated the expressions of stemness and anti-apoptotic genes by activating Rac1 and then phosphorylating Akt and NF-κB, thus leading to
oncogenesis of
melanoma stem cells. Our findings contribute new perspectives to
miRNA-regulated RNA editing in
tumor progression.