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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Chen AJ,Paik JH,Zhang H,Shukla SA,Mortensen R,Hu J,Ying H,Hu B,Hurt J,Farny N,Dong C,Xiao Y,Wang YA,Silver PA,Chin L,Vasudevan S,Depinho RA

doi

10.1101/gad.189001.112

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

1459-72

issue

13

eissn

0890-9369

issn

1549-5477

pii

26/13/1459

journal_volume

26

pub_type

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