STAR RNA-binding Protein Quaking Suppresses Cancer Via Stabilization of Specific MiRNA

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2012 Jul 4

PMID 22751500

Citations 76

Authors

An-Jou Chen

Ji-Hye Paik

Hailei Zhang

Sachet A Shukla

Richard Mortensen

Jian Hu

Haoqiang Ying

Baoli Hu

Jessica Hurt

Natalie Farny

Caroline Dong

Yonghong Xiao

Y Alan Wang

Pamela A Silver

Lynda Chin

Shobha Vasudevan

Ronald A DePinho

Affiliations

Soon will be listed here.

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.

Citing Articles

RNA-binding protein quaking: a multifunctional regulator in tumour progression.

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