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

Ning Li, Maryam Yousefi, Angela Nakauka-Ddamba, Fan Li, Lee Vandivier, Kimberly Parada, Dong Hun Woo, Shan Wang, Ammar S. Naqvi, Shilpa Rao, John Tobias, Ryan J. Cedeno, Gerard Minuesa, Katz Y, Trevor S. Barlowe, Alexander Valvezan, Sheila Shankar, Raquel P. Deering, Peter S. Klein, Shane T. JensenMichael G. Kharas, Brian D. Gregory, Zhengquan Yu, Christopher J. Lengner

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2440-2455
Number of pages16
JournalCell Reports
Volume13
Issue number11
DOIs
StatePublished - Dec 22 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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