RNAi‑mediated knockdown of E2F2 inhibits tumorigenicity of human glioblastoma cells

Nakahata,Adriana  M.; Suzuki,Daniela  E.; Rodini,Carolina  O.; Fiuza,Mayara  L.; Okamoto,Oswaldo  K.

doi:10.3892/ol.2014.2369

RNAi‑mediated knockdown of E2F2 inhibits tumorigenicity of human glioblastoma cells

Authors:
- Adriana M. Nakahata
- Daniela E. Suzuki
- Carolina O. Rodini
- Mayara L. Fiuza
- Oswaldo K. Okamoto
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Affiliations: Department of Neurology and Neurosurgery, Experimental Neurology Unit, Federal University of São Paulo, São Paulo 04023‑900, Brazil, Department of Neurology and Neurosurgery, Experimental Neurology Unit, Federal University of São Paulo, São Paulo 04023‑900, Brazil, Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo 05508‑090, Brazil
Published online on: July 22, 2014 https://doi.org/10.3892/ol.2014.2369
Pages: 1487-1491

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Abstract

In a previous genome‑wide expression profiling study, we identified E2F2 as a hyperexpressed gene in stem‑like cells of distinct glioblastoma multiforme (GBM) specimens. Since the encoded E2F2 transcription factor has been implicated in both tumor suppression and tumor development, we conducted a functional study to investigate the pertinence of E2F2 to human gliomagenesis. E2F2 expression was knocked down by transfecting U87MG cells with plasmids carrying a specific silencing shRNA. Upon E2F2 silencing, in vitro cell proliferation was significantly reduced, as indicated by a time‑course analysis of viable tumor cells. Anchorage‑independent cell growth was also significantly inhibited after E2F2 silencing, based on cell colony formation in soft agar. Subcutaneous and orthotopic xenograft models of GBM in nude mice also indicated inhibition of tumor development in vivo, following E2F2 silencing. As expression of the E2F2 gene is associated with glioblastoma stem cells and is involved in the transformation of human astrocytes, the present findings suggest that E2F2 is involved in gliomagenesis and could be explored as a potential therapeutic target in malignant gliomas.

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