# Characterization and Targeting of MiR-24 Network in Colitis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $346,500

## Abstract

PROJECT SUMMARY
MicroRNAs are small non-coding RNA molecules that have been implicated in the pathogenesis of different
human inflammatory diseases. Recent evidence indicates that manipulation of microRNA expression could
have therapeutic potential in inflammatory diseases of different etiologies. We and others have identified that
microRNAs are deregulated in Inflammatory Bowel Disease (IBD); however their role and functional
importance in IBD pathophysiology is not well understood. Our preliminary evidence revealed that miR-24
expression is specifically up-regulated in colonic biopsies from 2 cohorts of ulcerative colitis (UC), but not
Crohn's disease (CD) patients or patients with other GI diseases (irritable bowel syndrome, colorectal cancer).
Furthermore, miR-24 expression is higher in colonic biopsies from UC patients with active disease relative to
UC patients in remission. Although several microRNAs have been found to be deregulated in different
gastrointestinal (GI) diseases, our results demonstrate that miR-24 is specifically deregulated in UC,
suggesting an important role in UC pathogenesis. A key question in the microRNA field is the identification of
their direct gene targets. Here, we have followed an unbiased integrative computational and molecular analysis
and found that miR-24 is potentially involved in UC pathogenesis by regulating a gene network consisting of an
inflammatory (HFN4A-PPARγ-NF-κB) circuit by targeting directly HNFA, and an intestinal permeability control
mechanism, by modulating directly claudin-7, which affects the ERK and MMP signaling pathways. Thus, these
data suggest that miR-24 regulates inflammation and epithelial permeability, both key aspects of UC
pathogenesis. On the other hand, suppression of HNF4A and/or claudin-7 reinforced miR-24 increased
expression, suggesting the presence of a feedback loop network. This is the first evidence describing a
microRNA to act as a rheostat of the inflammatory response and intestinal permeability, through regulation of a
feedback loop network. Here, we will examine the novel hypothesis that the miR-24 network plays an important
role in UC pathophysiology by regulating inflammatory and intestinal permeability mechanisms. Based on
strong preliminary findings the following aims will address this overall hypothesis. Aim 1 will evaluate the role of
miR-24 – HNF4A network on controlling the inflammatory responses in UC. Aim 2 will characterize the
molecular mechanism of miR-24 on intestinal epithelial permeability. Use of human UC patient tissues will
confirm the UC relevance of the findings in aims 1 and 2. Aim 3 will examine the therapeutic potential of miR-
24 inhibition, by administering a novel chemically-stable miR-24 inhibitor (UCDI-1), in mouse models of
experimental colitis (in vivo) and in freshly isolated colonic explants from UC patients (ex vivo). Understanding
the miR-24 molecular network will not only provide novel insights on the role of miR-24 in UC pathophy...

## Key facts

- **NIH application ID:** 9982318
- **Project number:** 5R01DK110003-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** CHARALABOS POTHOULAKIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,500
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982318

## Citation

> US National Institutes of Health, RePORTER application 9982318, Characterization and Targeting of MiR-24 Network in Colitis (5R01DK110003-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9982318. Licensed CC0.

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