An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma.

摘要: By analyzing gene expression data in glioblastoma combination with matched microRNA profiles, we have uncovered a posttranscriptional regulation layer of surprising magnitude, comprising more than 248,000 (miR)-mediated interactions. These include ∼7,000 genes whose transcripts act as miR "sponges" and 148 that through alternative, nonsponge Biochemical analyses cell lines confirmed this network regulates established drivers tumor initiation subtype implementation, including PTEN, PDGFRA, RB1, VEGFA, STAT3, RUNX1, suggesting these interactions mediate crosstalk between canonical oncogenic pathways. siRNA silencing 13 miR-mediated PTEN regulators, locus deletions are predictive variability, was sufficient to downregulate 3'UTR-dependent manner increase growth rates. Thus, provide mechanistic, experimentally validated rationale for the loss large number glioma samples an intact locus.