期刊
GENES & DEVELOPMENT
卷 32, 期 15-16, 页码 1020-1034出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.314369.118
关键词
LIN28B; IMP1; intestinal tumorigenesis; post-transcriptional regulation; ribosome profiling
资金
- National Institutes of Health (NIH) [R01 DK056645]
- NIH [P30DK050306, K01 DK100485, F32DK107052, T32CA1152999, R35 GM124976, R03DK114463]
- Crohn's and Colitis Foundation Career Development Award
- American Cancer Society
- Lustgarten Family Colon Cancer Fund
- National Institute of General Medical Sciences [T32GM008216-29]
- Human Genetics Institute of New Jersey
- Rutgers University
- Children's Hospital of Philadelphia Research Institute
RNA-binding proteins (RBPs) are expressed broadly during both development and malignant transformation, yet their mechanistic roles in epithelial homeostasis or as drivers of tumor initiation and progression are incompletely understood. Here we describe a novel interplay between RBPs LIN28B and IMP1 in intestinal epithelial cells. Ribosome profiling and RNA sequencing identified IMP1 as a principle node for gene expression regulation downstream from LIN28B. In vitro and in vivo data demonstrate that epithelial IMP1 loss increases expression of WNT target genes and enhances LIN28B-mediated intestinal tumorigenesis, which was reversed when we overexpressed IMP1 independently in vivo. Furthermore, IMP1 loss in wild-type or LIN28B-overexpressing mice enhances the regenerative response to irradiation. Together, our data provide new evidence for the opposing effects of the LIN28B-IMP1 axis on post-transcriptional regulation of canonical WNT signaling, with implications in intestinal homeostasis, regeneration and tumorigenesis.
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