A recent study shows that impaired miRNA editing leads to increased glioma cell migration and invasion (J. Clin. Invest. 122, 4059–4076).

Yukti Choudhury et al. investigated the modification of the miR-376 cluster, which is known to be subject to RNA editing, in human glioma samples and glioma cell lines. There was less editing of miR-376 cluster transcripts in gliomas compared with normal brain tissue samples. High-grade gliomas showed higher amounts of the unedited form of the cluster miRNA miR-376a*, which correlated with the extent of tumor invasion.

Introduction of the unedited miR-376a* into glioma cells promoted cell invasion and migration, and injection of glioma cells expressing the unedited miRNA into mouse brains led to the development of more invasive tumors than cells expressing edited miR-376a*. The authors compared the genes regulated by the two forms of miR-376a* using microarray analyses, homing in on two candidates: RAP2A, a target of unedited miR-376a*, and AMFR, a target of edited miR-376a*. Downregulation of RAP2A and upregulation of AMFR led to increased migration of glioma cells, and these gene expression changes were also observed in human glioma samples and correlated with the expression of unedited miR-376a*.

These new findings highlight the importance of RNA editing in cancer and also indicate that unedited miR-376a* might be a therapeutic target in glioblastoma.