Abstract 5621: MicroRNA 203 modulates glioma cell migration and invasion by targeting ROBO1

Abstract

Abstract MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. A potential role for miRNAs in malignancy has been suggested by the location of the genes for several miRNAs at sites of translocation breakpoints or deletions linked to a specific neoplastic state. Allelic deletion on chromosome 14q plays an important role in the pathogenesis of GBM and was thought to harbor multiple tumor suppressor genes associated with GBM, a region which also encodes mir-203. Real-time PCR and insitu hybridization showed decreased levels of mir203 expression in anaplastic astrocytoma and glioblastoma tissues and cell lines. Exogenous expression of mir-203 using a plasmid expressing mir-203 precursor (pmir-203) suppressed cell invasion and migration in SNB19 glioblastoma cell line and 4910 xenograft cells. We determined that one relevant target of miR-203 was ROBO1, since miR-203 expression decreased mRNA and protein levels as determined by RT-PCR and western blot analysis. Moreover, cotransfection experiments using luciferase-based transcription reporter assay have shown direct regulation of ROBO1 3α-UTR regions by miR-203 which was significantly abrogated when mutating the predicted miR-203 seed regions in the pMIR-REPORT UTR constructs, thereby validating the direct interaction between miR-203 and the ROBO1 3α-UTRs. Concordantly, over expressing ROBO1 expression construct with no mir-203 binding site blocked pmir-203 mediated suppression of migration and invasion. Taken together these studies demonstrate that up regulation of Robo1 in response to the decrease in mir-203 in glioma cells is responsible for glioma tumor cell migration and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5621. doi:1538-7445.AM2012-5621