Please use this identifier to cite or link to this item:
DC FieldValue
dc.titleAttenuated adenosine-to-inosine editing of microRNA-376a*promotes invasiveness of glioblastoma cells
dc.contributor.authorChoudhury, Y.
dc.contributor.authorTay, F.C.
dc.contributor.authorLam, D.H.
dc.contributor.authorSandanaraj, E.
dc.contributor.authorTang, C.
dc.contributor.authorAng, B.-T.
dc.contributor.authorWang, S.
dc.identifier.citationChoudhury, Y., Tay, F.C., Lam, D.H., Sandanaraj, E., Tang, C., Ang, B.-T., Wang, S. (2012-11-01). Attenuated adenosine-to-inosine editing of microRNA-376a*promotes invasiveness of glioblastoma cells. Journal of Clinical Investigation 122 (11) : 4059-4076. ScholarBank@NUS Repository.
dc.description.abstractIn the human brain, microRNAs (miRNAs) from the microRNA-376 (miR-376) cluster undergo programmed "seed" sequence modifications by adenosine-to-inosine (A-to-I) editing. Emerging evidence suggests a link between impaired A-to-I editing and cancer, particularly in high-grade gliomas. We hypothesized that disruption of A-to-I editing alters expression of genes regulating glioma tumor phenotypes. By sequencing the miR-376 cluster, we show that the overall miRNA editing frequencies were reduced in human gliomas. Specifically in high-grade gliomas, miR-376a*accumulated entirely in an unedited form. Clinically, a significant correlation was found between accumulation of unedited miR-376a*and the extent of invasive tumor spread as measured by magnetic resonance imaging of patient brains. Using both in vitro and orthotopic xenograft mouse models, we demonstrated that the unedited miR-376a*promoted glioma cell migration and invasion, while the edited miR-376a*suppressed these features. The effects of the unedited miR-376a*were mediated by its sequence-dependent ability to target RAP2A and concomitant inability to target AMFR. Thus, the tumor-dependent introduction of a single base difference in the miR-376a*sequence dramatically alters the selection of its target genes and redirects its function from inhibiting to promoting glioma cell invasion. These findings uncover a new mechanism of miRNA deregulation and identify unedited miR-376a*as a potential therapeutic target in glioblastoma cells.
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.sourcetitleJournal of Clinical Investigation
Appears in Collections:Staff Publications

Show simple item record
Files in This Item:
There are no files associated with this item.

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.