Title of article :
In Vivo Identification of Tumor- Suppressive PTEN ceRNAs in an Oncogenic BRAF-Induced Mouse Model of Melanoma
Author/Authors :
Florian A. Karreth، نويسنده , , Yvonne Tay، نويسنده , , Daniele Perna، نويسنده , , Ugo Ala، نويسنده , , Shen Mynn Tan، نويسنده , , Alistair G. Rust، نويسنده , , Gina DeNicola، نويسنده , , Kaitlyn A. Webster، نويسنده , , Dror Weiss، نويسنده , , Pedro A. Perez-Mancera، نويسنده , , Michael Krauthammer، نويسنده , , Ruth Halaban، نويسنده , , Paolo Provero، نويسنده , , David J. Adams and ...[et al.]، نويسنده , , David A. Tuveson، نويسنده , , Pier Paolo Pandolfi، نويسنده ,
Issue Information :
هفته نامه با شماره پیاپی سال 2011
Pages :
14
From page :
382
To page :
395
Abstract :
We recently proposed that competitive endogenous RNAs (ceRNAs) sequester microRNAs to regulate mRNA transcripts containing common microRNA recognition elements (MREs). However, the functional role of ceRNAs in cancer remains unknown. Loss of PTEN, a tumor suppressor regulated by ceRNA activity, frequently occurs in melanoma. Here, we report the discovery of significant enrichment of putative PTEN ceRNAs among genes whose loss accelerates tumorigenesis following Sleeping Beauty insertional mutagenesis in a mouse model of melanoma. We validated several putative PTEN ceRNAs and further characterized one, the ZEB2 transcript. We show that ZEB2 modulates PTEN protein levels in a microRNA-dependent, protein coding-independent manner. Attenuation of ZEB2 expression activates the PI3K/AKT pathway, enhances cell transformation, and commonly occurs in human melanomas and other cancers expressing low PTEN levels. Our study genetically identifies multiple putative microRNA decoys for PTEN, validates ZEB2 mRNA as a bona fide PTEN ceRNA, and demonstrates that abrogated ZEB2 expression cooperates with BRAFV600E to promote melanomagenesis.
Journal title :
CELL
Serial Year :
2011
Journal title :
CELL
Record number :
1020879
Link To Document :
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