RNA modifications are increasingly being recognized as critical players in cancer. While adenosine-to-inosine RNA editing is consistently deregulated in cancer, we are still unable to draw a straight line connecting transcript-specific editing and carcinogenesis. The findings by Choudhury et al. in this issue of the JCI bridge this gap by mechanistically implicating underediting of miR-376a* in promoting glioma invasiveness through redirection of its mRNA targets. Moreover, RAP2A and AMFR convincingly emerge as key regulators of glioma migration and invasion affected by deregulated microRNA editing. Being inherently malleable, epigenetic mechanisms may provide feasible targets for therapeutic benefit.
Dan Dominissini, Ninette Amariglio, Gideon Rechavi
Mature miRNA-376a* seed sequence is unedited in high-grade gliomas, consequently promoting glioma cell migration and invasion through altered target specificity.