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: 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
• Journal: Genes & development (Genes Dev) Vol. 26 Issue 13 Pg. 1459-72 (Jul 01 2012) ISSN: 1549-5477 [Electronic] United States
• PMID: 22751500 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN20a microRNA, human
• MicroRNAs
• Mirn20 microRNA, mouse
• QKI protein, human
• Qk protein, mouse
• RNA-Binding Proteins
• Tumor Suppressor Protein p53

Topics

• Animals
• Cell Line
• Glioblastoma (genetics, metabolism)
• Humans
• Mice
• MicroRNAs (genetics, metabolism)
• RNA Stability
• RNA-Binding Proteins (genetics, metabolism)
• Signal Transduction
• Tumor Suppressor Protein p53 (genetics, metabolism)