Biotechnology Commons^™

Star Rna-Binding Protein Quaking Suppresses Cancer Via Stabilization Of Specific Mirna, Natalie Farny, An-Jou Chen, Ji-Hye Paik, Hailei Zhang, Sachet Shukla, Richard Mortensen, Jian Hu, Haoqiang Ying, Baoli Hu, Jessica Hurt, Caroline Dong, Yonghong Xiao, Y. Wang, Pamela Silver, Lynda Chin, Shobha Vasudevan, Ronald Depinho

Natalie G. Farny

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 …