STAR RNA-binding protein, Quaking, suppresses cancer via regulation of microRNA

MicroRNAs have emerged as major genetic elements in the genesis and suppression of cancer. Here, multi-dimensional cancer genome analysis and validation has defined a novel Glioblastoma Multiforme (GBM) tumor suppressor pathway and mechanism of action centered on Quaking (QK), a member of the STAR family of RNA-binding proteins. Combined functional, biochemical and computational studies establish that p53 directly regulates QK gene expression, QK protein binds and stabilizes miR-20a of the cancer-relevant miR-17-92 cluster, and miR-20a in turn functions to regulate TGFβR2 and the TGFβ signaling network. Linkage of these pathway components is supported by their genome and expression status across GBM specimens and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QK-miR-20a axis expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.