# The LIN28b-Let7-IMP1 axis in colonic epithelial biology

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $370,961

## Abstract

PROJECT SUMMARY
The intestinal epithelium is in a dynamic equilibrium of proliferation, differentiation and apoptosis along the
crypt-villus gradient. Normal intestinal homeostasis is disturbed during states of infection, inflammation and
malignant transformation (adenomatous polyps, colorectal cancer). The pathogenesis of sporadic colorectal
cancer involves distinct pathways with characteristic genomic and genetic alterations. Despite significant
advances in leveraging our understanding of these pathways for diagnostic, prognostic, and therapeutic
strategies, colorectal cancer (CRC) remains a leading cause of cancer-related mortality. This underscores a
specific need to identify and understand novel, therapeutically tractable pathways in intestinal homeostasis that
may drive CRC. Our work has introduced and elucidated the novel role of mRNA binding proteins in
intestinal/colonic epithelial homeostasis, as well as aberrations including hyperproliferation, altered metabolism
and transformation. LIN28B, an mRNA binding protein, also critical in embryonic stem cells, post-
transcriptionally regulates the let-7 microRNA family and results in suppression of differentiation. In turn, Let-7
microRNAs have diverse mRNA targets, including IMP1 (Igf2 mRNA binding protein-1), another mRNA binding
protein. We have demonstrated that LIN28B and IMP1 separately drive tumor-initiating cell phenotypes
associated with their roles in regulating proliferation and differentiation during normal homeostasis; however, it
remains unclear if LIN28B-mediated hyperproliferation, altered differentiation, and associated tumorigenesis
requires IMP1. In addition, it remains unknown if the tumor promoting or metastatic roles of IMP1 depend
entirely on its regulation by Let-7 downstream of LIN28B. Our overarching hypothesis of this proposal is that
LIN28B and IMP1 comprise cooperative roles in controlling post-transcriptionally the pathways (some known)
associated with epithelial cell fate, which may favor malignant transformation. We will pursue this hypothesis
through the following interrelated Specific Aims: Aim 1: To evaluate the interdependence of LIN28B and
IMP1 in proliferation, differentiation, and malignant transformation in vivo. Aim 2: To determine and validate
common and divergent pathways mediated by LIN28B and IMP1 via RNA-Sequencing (“transcriptome”) and
ribosome profiling (“translatome”) in vivo. Aim 3: To evaluate Let-7 dependent regulation of IMP1 to promote
hyperproliferation and metastasis.

## Key facts

- **NIH application ID:** 9829558
- **Project number:** 5R01DK056645-20
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Anil K Rustgi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,961
- **Award type:** 5
- **Project period:** 2000-03-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829558

## Citation

> US National Institutes of Health, RePORTER application 9829558, The LIN28b-Let7-IMP1 axis in colonic epithelial biology (5R01DK056645-20). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9829558. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*