TY - JOUR
T1 - The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine
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.
N1 - Funding Information:
We thank members of the Rustgi laboratory for helpful discussions, and Dr. Dan Dixon for critical reading of this manuscript. We thank Dr. Kay Lund for valuable input. Financial support was provided by National Institutes of Health (NIH) R01 DK056645 (to P.C., R.M., S.F.A., K.E.H., and A.K.R.), NIH P30DK050306 and its pilot grant program (to K.E.H. and A.K.R.), NIH K01 DK100485 (to K.E.H.), a Crohn’s and Colitis Foundation Career Development Award (to K.E.H.), NIH F32DK107052 (to S.F.A.), NIH T32CA1152999 (to S.F.A.), the American Cancer Society (to A.K.R.), the Lustgarten Family Colon Cancer Fund (to A.K.R.), NIH R35 GM124976 (to S.L.,
Funding Information:
We thank members of the Rustgi laboratory for helpful discussions, and Dr. Dan Dixon for critical reading of this manuscript. We thank Dr. Kay Lund for valuable input. Financial support was provided by National Institutes of Health (NIH) R01 DK056645 (to P.C., R.M., S.F.A., K.E.H., and A.K.R.), NIH P30DK050306 and its pilot grant program (to K.E.H. and A.K.R.), NIH K01 DK100485 (to K.E.H.), a Crohn’s and Colitis Foundation Career Development Award (to K.E.H.), NIH F32DK107052 (to S.F.A.), NIH T32CA1152999 (to S.F.A.) (to S.F.A.), the American Cancer Society (to A.K.R.), the Lustgarten Family Colon Cancer Fund (to A.K.R.), NIH R35 GM124976 (to S.L. H.R.S.W., and P.S.), National Institute of General Medical Sciences T32GM008216-29 (to S.W.F.), start-up funds from the Human Genetics Institute of New Jersey and Rutgers University (to S.L., H.R.S.W., and P.S.), NIH R03DK114463 (to K.E.H.), and startup funds from the Childrens Hospital of Philadelphia Research Institute (to K.E.H.).
Publisher Copyright:
© 2018 Chatterji et al.
PY - 2018/8/1
Y1 - 2018/8/1
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.
KW - IMP1
KW - Intestinal tumorigenesis
KW - LIN28B
KW - Post-transcriptional regulation
KW - Ribosome profiling
UR - http://www.scopus.com/inward/record.url?scp=85051279188&partnerID=8YFLogxK
U2 - 10.1101/gad.314369.118
DO - 10.1101/gad.314369.118
M3 - Article
C2 - 30068703
AN - SCOPUS:85051279188
VL - 32
SP - 1020
EP - 1034
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 15-16
ER -