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Title: MiR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme
Authors: Yin, D.
Ogawa, S.
Kawamata, N.
Leiter, A.
Ham, M.
Li, D.
Doan, N.B.
Said, J.W.
Black, K.L.
Phillip Koeffler, H. 
Keywords: EGFR
genomic profiling
glioblastoma multiforme
Issue Date: 28-Feb-2013
Citation: Yin, D., Ogawa, S., Kawamata, N., Leiter, A., Ham, M., Li, D., Doan, N.B., Said, J.W., Black, K.L., Phillip Koeffler, H. (2013-02-28). MiR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme. Oncogene 32 (9) : 1155-1163. ScholarBank@NUS Repository.
Abstract: Chromosome 1p36.23 is frequently deleted in glioblastoma multiforme (GBM). miR-34a localizes in this region. Our experiments found that miR-34a was often deleted and epidermal growth factor receptor (EGFR) was frequently amplified in genomic DNA of 55 GBMs using single-nucleotide polymorphism DNA microarray. Notably, we found that the mean survival time was significantly shortened for patients whose GBMs had both EGFR amplification and miR-34a deletion. Expression of miR-34a was significantly lower in GBM samples compared with normal brain tissue. Forced expression of miR-34a in GBM cells decreased their ability to migrate and profoundly decreased their levels of cyclin-A1, -B1, -D1, and -D3, as well as cyclin-dependent kinase and increased expression of cyclin kinase inhibitor proteins (p21, p27). Also, human GBM cells (U251) stable overexpressing mir-34a formed smaller tumors when growing as xenografts in immunodeficient mice compared with wild-type U251 GBM cells. Furthermore, the protein expression of EGFR decreased in the cells with forced overexpression of miR-34a. Additional studies showed that mir-34a targeted Yin Yang-1 (YY1) and YY1 is a transcription factor that can stimulate the expression of EGFR. Thus, our data suggest that miR-34a acts as a tumor suppressor by inhibiting growth of GBM cells in vitro and in vivo associated with moderating the expression of cell-cycle proteins and EGFR. Moreover, we discovered for the first time that both deletion of miR-34a and amplification of EGFR were associated with significantly decreased overall survival of GBM patients. © 2013 Macmillan Publishers Limited All rights reserved.
Source Title: Oncogene
ISSN: 09509232
DOI: 10.1038/onc.2012.132
Appears in Collections:Staff Publications

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