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

• DOI: 10.1016/j.celrep.2015.11.022
• Publication Date: 2015-12-12T11:06:06Z
• Authors: Ning Li; Maryam Yousefi; Angela Nakauka-Dd...; 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. Jensen; Michael G. Kharas; Brian D. Gregory; Zhengquan Yu; Christopher J. Le...
• Keywords: 0301 basic medicine; QH301-705.5; Mice, Nude; Mice, Transgenic; Nerve Tissue Proteins; Mechanistic Target of Rapamycin Complex 1; Protein Serine-Threonine Kinases; Mice; 03 medical and health sciences; Genes, Reporter; Animals; Humans; Biology (General); Intestinal Mucosa; Mice, Knockout; PTEN Phosphohydrolase; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; HCT116 Cells; 3. Good health; Disease Models, Animal; Cell Transformation, Neoplastic; Multiprotein Complexes; Female; Colorectal Neoplasms; Proto-Oncogene Proteins c-akt

Members of the Msi family RNA-binding proteins have recently emerged as potent oncoproteins in a range malignancies. MSI2 is highly expressed hematopoietic cancers, where it required for disease maintenance. In contrast to system, colorectal cancers can express both members, MSI1 and MSI2. Here, we demonstrate that, intestinal epithelium, Msi1 Msi2 analogous oncogenic effects. Further, comparison Msi1/2-induced gene expression programs transcriptome-wide analyses Msi1/2-RNA-binding targets reveal significant functional overlap, including induction PDK-Akt-mTORC1 axis. Ultimately, that concomitant loss function MSI members sufficient abrogate growth human cancer cells, deletion inhibits tumorigenesis several mouse models cancer. Our findings act functionally redundant ontogeny cancers.