Suppression of RNA editing by miR-17 inhibits the stemness of melanoma stem cells

• Published in: Molecular therapy. Nucleic acids 2022-03, Vol.27, p.439-455
• Main Authors: Zhang, Yu, Yang, Xiaoyuan, Cui, Yalei, Zhang, Xiaobo
• Format: Article
• Language: English
• Subjects: melanoma stem cells; miR-17; Original; Rac1/Akt/NF-κB pathway; RNA editing; stemness
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2021.12.021

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. [Display omitted] MiR-17 inhibits RNA editing to achieve post-transcriptional regulation of DOCK2, leading to the suppression of the stemness of melanoma stem cells. Our findings indicate that miRNA-regulated RNA editing plays important roles in tumor progression and that miR-17, a tumor suppressor, may be a potential therapeutic target for the treatment of melanoma.