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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.
This article has been published Open Access under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
Li, N., Yousefi, M., Nakauka-Ddamba, A., Li, F., Vandivier, L., Parada, K., Woo, D., Wang, S., Naqvi, A. S., Rao, S., Tobias, J., Cedeno, R. J., Minuesa, G., Y, K., Barlowe, T. S., Valvezan, A. J., Shankar, S., Deering, R. R., Klein, P. S., Jensen, S. T., Kharas, M. G., Gregory, B. D., Yu, Z., & Lengner, C. J. (2015). The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins. Cell Reports, 13 (11), 2440-2455. http://dx.doi.org/10.1016/j.celrep.2015.11.022
Additional FilesTable S1_The Msi Family of RNA-binding proteins.xls (472 kB)
Table S2_The Msi Family of RNA-binding proteins.xls (419 kB)
Table S3_The Msi Family of RNa-binding proteins.xlsx (58 kB)
Table S4_The Msi Family of RNA-binding proteins.xlsx (228 kB)
Table S5_The Msi Family of RNA-binding proteins.pdf (1052 kB)
Table S6_The Msi Family of RNA-binding proteins.xlsx (67 kB)
Date Posted:10 July 2017
This document has been peer reviewed.