The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

Priya Chatterji, Kathryn E. Hamilton, Shun Liang, Sarah F. Andres, H. R.Sagara Wijeratne, Rei Mizuno, Lauren A. Simon, Philip D. Hicks, Shawn W. Foley, Jason R. Pitarresi, Andres J. Klein-Szanto, Amanda T. Mah, Laurianne van Landeghem, Brian D. Gregory, Christopher J. Lengner, Blair B. Madison, Premal Shah, Anil K. Rustgi

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1020-1034
Number of pages15
JournalGenes and Development
Volume32
Issue number15-16
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

Keywords

  • IMP1
  • Intestinal tumorigenesis
  • LIN28B
  • Post-transcriptional regulation
  • Ribosome profiling

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine'. Together they form a unique fingerprint.

Cite this