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Background   SOX2  is a key gene implicated in maintaining the stemness of embryonic and adult stem cells.  SOX2  appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of  SOX2  in GBM has not yet been defined.    Results  We show that knockdown of the  SOX2  gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the  SOX2  response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883  SOX2  binding regions in the GBM cancer genome.  SOX2  binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312  SOX2  binding regions. Microarray analysis identified 489 genes whose expression altered in response to  SOX2  knockdown. Interesting findings include that  SOX2  regulates the expression of SOX family proteins  SOX1  and  SOX18 , and that  SOX2  down regulates  BEX1  (brain expressed X-linked 1) and  BEX2  (brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by  SOX2 , including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and  SOX2  form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.    Conclusions  We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the  SOX2  response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of  SOX2  in carcinogenesis and serves as a useful resource for the research community.

The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis