Poster abstracts

Poster number 60 submitted by Sung-Suk Suh

c-Myc-Activated miR-25/32 function as Tumor Suppressor by Restoring p53 Activity in Glioblastoma mutiforme (GBM)

Sung-Suk Suh (MVIMG), Flavia Pichiorri (MVIMG), Ji-Young Yoo (Department of Neurological Surgery)

Abstract:
Glioblastoma multiforme (GBM) is the most aggressive and frequent histological type of brain tumor. Despite recent advances in treatment, patient survival remains very poor, signifying an inevitable necessity for development of treatment strategies that provide the most effective and selective therapies by targeting molecular defects in the tumors. Here, we provide evidence that miR-25 and -32, which are overexpressed in glioblastomas, modulate p53 activity by targeting MDM2 and TSC1, and promote apoptotic cell death. Further, we demonstrate that miR-25 and -32 can be transcriptionally activated by c-Myc that in a p53-dependent manner. All together these data suggest that miR-25 and -32 are positive regulators of p53 underscoring their role in tumorigenesis in glioblastoma.

References:
Ard, P.G., Chatterjee,C., Kunjibettu,S., Adside, L.R., Gralinski, L.E., McMahon, S.B. Transcriptional Regulation of the mdm2 Oncogene by p53 Requires TRRAP Acetyltransferase Complexes. (2000). MCM 22, 5650-5661.
Arnold, J., Zhaohui, F., Tak, W.M., Han, Y., Shengkan, J. (2006). Coordination and communication between the p53 and IGF—AKT-TOR signal transduction pathway. Genes& Dev 20, 267-275.
Beveridge, N.V., Gardiner, E., Carroll, A.P., Tooney, P.A., Cairns, M.J. (2010). Schisophrenia is associated with an increase in cortical miRNA biogenesis. Molecular Psychiatry 15, 1176-1189.

Keywords: miRNA, p53, MDM2