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

doi:10.1101/gad.314369.118

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 journal › Article › peer-review

16 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 language	English (US)
Pages (from-to)	1020-1034
Number of pages	15
Journal	Genes and Development
Volume	32
Issue number	15-16
DOIs	https://doi.org/10.1101/gad.314369.118
State	Published - Aug 1 2018
Externally published	Yes

Keywords

IMP1
Intestinal tumorigenesis
LIN28B
Post-transcriptional regulation
Ribosome profiling

ASJC Scopus subject areas

General Medicine

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10.1101/gad.314369.118

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Chatterji, P., Hamilton, K. E., Liang, S., Andres, S. F., Wijeratne, H. R. S., Mizuno, R., Simon, L. A., Hicks, P. D., Foley, S. W., Pitarresi, J. R., Klein-Szanto, A. J., Mah, A. T., van Landeghem, L., Gregory, B. D., Lengner, C. J., Madison, B. B., Shah, P., & Rustgi, A. K. (2018). The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine. Genes and Development, 32(15-16), 1020-1034. https://doi.org/10.1101/gad.314369.118

Chatterji, P, Hamilton, KE, Liang, S, Andres, SF, Wijeratne, HRS, Mizuno, R, Simon, LA, Hicks, PD, Foley, SW, Pitarresi, JR, Klein-Szanto, AJ, Mah, AT, van Landeghem, L, Gregory, BD, Lengner, CJ, Madison, BB, Shah, P & Rustgi, AK 2018, 'The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine', Genes and Development, vol. 32, no. 15-16, pp. 1020-1034. https://doi.org/10.1101/gad.314369.118

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

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.",

keywords = "IMP1, Intestinal tumorigenesis, LIN28B, Post-transcriptional regulation, Ribosome profiling",

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

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doi = "10.1101/gad.314369.118",

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AU - Chatterji, Priya

AU - Hamilton, Kathryn E.

AU - Liang, Shun

AU - Andres, Sarah F.

AU - Wijeratne, H. R.Sagara

AU - Mizuno, Rei

AU - Simon, Lauren A.

AU - Hicks, Philip D.

AU - Foley, Shawn W.

AU - Pitarresi, Jason R.

AU - Klein-Szanto, Andres J.

AU - Mah, Amanda T.

AU - van Landeghem, Laurianne

AU - Gregory, Brian D.

AU - Lengner, Christopher J.

AU - Madison, Blair B.

AU - Shah, Premal

AU - Rustgi, Anil K.

PY - 2018/8/1

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N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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