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E-GEOD-64388 - Transformation of the intestinal epithelium by the MSI2 RNA binding protein

Status
Released on 20 December 2014, last updated on 2 January 2015
Organism
Mus musculus
Samples (4)
Protocols (1)
Description
The MSI2 RNA binding protein has recently emerged as a potent oncogene playing key roles in hematopoietic stem cell homeostasis and malignant hematopoiesis. Here we demonstrate that MSI2 is expressed in the intestinal stem cell compartment, that its expression is elevated in colorectal adenocarcinomas, and that MSI2 loss of function abrogates colorectal cancer cell growth. We thus examined the oncogenic consequences of MSI2 gain of function in the intestinal epithelium with a drug inducible mouse model. Strikingly, MSI2 induction alone was sufficient to phenocopy the majority of morphological and molecular consequences of acute loss of the APC tumor suppressor in the intestinal epithelium. We demonstrate that this phenotype is independent of both the activation of the other oncogenic Musashi family member, Msi1, and of canonical Wnt pathway activation. Transcriptome-wide RNA-binding analysis indicates that MSI2 acts as a pleiotropic inhibitor of known intestinal tumor suppressors including Lrig1, Bmpr1a, Cdkn1a, and Pten. Finally, we demonstrate that inhibition of the PDK-AKT-mTORC1 axis downstream of Pten rescues oncogenic consequences of MSI2 induction. Taken together, our findings identify MSI2 as a central component in an unappreciated oncogenic pathway promoting intestinal transformation. 2 wild-type samples, 2 TRE-Msi2 samples
Experiment type
other 
Contacts
Fan Li <fanli@mail.med.upenn.edu>, Brian D Gregory, Christopher J Lengner
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-64388.idf.txt
Sample and data relationshipE-GEOD-64388.sdrf.txt
Additional data (1)E-GEOD-64388.additional.1.zip
Links