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

Aim: 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. Method: Here we describe a novel interplay between RBPsLIN28B and IMP1 in intestinal epithelial cells. Ribosome-profiling and RNA-sequencing identifies IMP1 as a principle nodefor gene expression regulation downstream of LIN28B. Results: 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 enhancesthe regenerative response to irradiation. Conclusions: 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. Ribosome-footprinting and RNA-seq samples from LIN28B OE SW480 cells and LIN28B OE+IMP1-/- knockout cells