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Publication : The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins.

First Author  Li N Year  2015
Journal  Cell Rep Volume  13
Issue  11 Pages  2440-2455
PubMed ID  26673327 Mgi Jnum  J:273980
Mgi Id  MGI:6274059 Doi  10.1016/j.celrep.2015.11.022
Citation  Li N, et al. (2015) The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins. Cell Rep 13(11):2440-2455
abstractText  Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers.
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