Investigating microRNA-transcription factor mediated regulatory network in glioblastoma

Glioblastoma is the most aggressive form of brain cancer. Transcriptional aberrations may play an important role in etiology of glioblastoma, which might be caused through genomic alterations: nucleotide mutation, copy number variation, DNA mythelation. Here, we explored another possible mechanism involving cooperative deregulation of microRNAs (miRNAs) and transcription factors (TFs). Several miRNA-TF mediated regulatory modules have been verified. Under the hypothesis that miRNAs and TFs might have a combinational regulatory effect on glioblastoma genes, we searched glioblastoma-specific regulatory network by integration of miRNAs and TFs. Fifty-four feed-forward loops (FFLs) were identified among the glioblastoma related miRNAs, genes and TFs. Then, a novel miRNA-TF regulatory network for glioblastoma was constructed by converging those FFLs, in which PIK3R1, PTEN, C21ORF29, GOPC, LMX1A and LRP2 served as core genes. This study shed light on the regulatory mechanisms of glioblastoma related genes. It represents the first investigation of a miRNA-TF regulatory network for glioblastoma.