title: STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
abstract: Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI protein associates with and leads to the stabilization of miR-20a; miR-20a, in turn, regulates TGFβR2 and the TGFβ signaling network. This pathway circuitry is substantiated by in silico epistasis analysis of its components in the human GBM TCGA (The Cancer Genome Atlas Project) collection and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QKI-miR-20a-TGFβ pathway 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.
authors: Belfer Institute for Applied Cancer Science, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: An-Jou
authors: AJ
authors: Chen
authors: Ji-Hye
authors: JH
authors: Paik
authors: Hailei
authors: H
authors: Zhang
authors: Sachet A
authors: SA
authors: Shukla
authors: Richard
authors: R
authors: Mortensen
authors: Jian
authors: J
authors: Hu
authors: Haoqiang
authors: H
authors: Ying
authors: Baoli
authors: B
authors: Hu
authors: Jessica
authors: J
authors: Hurt
authors: Natalie
authors: N
authors: Farny
authors: Caroline
authors: C
authors: Dong
authors: Yonghong
authors: Y
authors: Xiao
authors: Y Alan
authors: YA
authors: Wang
authors: Pamela A
authors: PA
authors: Silver
authors: Lynda
authors: L
authors: Chin
authors: Shobha
authors: S
authors: Vasudevan
authors: Ronald A
authors: RA
authors: Depinho
mesh_terms: D000818:Animals; D002460:Cell Line; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C534451:MIRN20a microRNA, human; D035683:MicroRNAs; C532375:Mirn20 microRNA, mouse; C490832:QKI protein, human; C098217:Qk protein, mouse; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53