RNAi-mediated knockdown of inhibits tumorigenicity of human glioblastoma cells.

In a previous genome-wide expression profiling study, we identified 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 to human gliomagenesis. expression was knocked down by transfecting U87MG cells with plasmids carrying a specific silencing shRNA. Upon silencing, 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 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 following silencing. As expression of the 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.