# Project 1: Epithelial Adherens Junctions Regulate Colon Cell Behavior through RNAi and IncRNAs

> **NIH NIH P20** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $224,250

## Abstract

Project 1 – Project Summary
Compromised epithelial integrity is a hallmark of gastrointestinal diseases, such as inflammatory bowel disease
and colon cancer, which is the third most prevalent and lethal form of cancer. The high incidence rates of these
diseases suggest that we still do not fully understand the underlying mechanisms connecting epithelial
architecture and cell behavior. Recently, we discovered a mechanism that links epithelial tissue integrity with the
RNA interference (RNAi) machinery and with miRNA regulation. In particular, we have shown that the adherens
junctions, which is an essential architectural component of the cell, recruit the microprocessor and the RNAi-
induced silencing complex (RISC), the core components of the RNAi machinery, as well as a specific set of
miRNAs, in colon epithelial cells. This interaction occurs through PLEKHA7, a novel partner of the E-cadherin
cell-cell adhesion complex. PLEKHA7 loss results in compromised epithelial integrity, decreased levels and
activity of a set of miRNAs and in increased anchorage-independent growth, an indicator of epithelial
transformation. Importantly, our preliminary data show extensive mis-localization or loss of PLEKHA7 in colon
cancer cell lines and tumor patient samples. Interestingly, an RNA-CLIP experiment followed by RNA sequencing
revealed association of PLEKHA7 with a large set of long non-coding RNAs (lncRNAs). LncRNAs can interact
with miRNAs and the RNAi machinery in multiple ways and a number of them has been implicated in intestinal
diseases. However, our knowledge on lncRNA regulation and function is still limited. Our preliminary data show
that PLEKHA7 loss results in dysregulation of a number of these lncRNAs, including upregulation of MIR17HG,
which is a known oncogenic lncRNA and a strong promoter of cellular transformation. We hypothesize that the
adherens junctions recruit and regulate the RNAi machinery and lncRNAs to maintain colon epithelial
homeostasis. We will examine our hypothesis under the following Specific Aims: 1) PLEKHA7 suppresses
MIR17HG by recruiting RISC and miRNAs at the adherens junctions; 2) PLEKHA7 maintains the normal colon
epithelial phenotype by suppressing MIR17HG. This study is significant, since it provides a missing mechanistic
link between epithelial architecture and cell behavior, as well as a new unexpected localized regulation of
lncRNAs, which may be critical the maintenance of the normal colonic phenotype. The proposed work is
innovative, because it tethers two previously unrelated fields, cell-cell adhesion and lncRNA biology. The impact
of the study is that it will advance our understanding of the underlying mechanistic causes of intestinal diseases
and will lay the foundation for the systematic interrogation of the newly discovered connection between the
adherens junctions, the RNAi machinery and lncRNAs.

## Key facts

- **NIH application ID:** 9853389
- **Project number:** 1P20GM130457-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Antonis Kourtidis
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $224,250
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853389

## Citation

> US National Institutes of Health, RePORTER application 9853389, Project 1: Epithelial Adherens Junctions Regulate Colon Cell Behavior through RNAi and IncRNAs (1P20GM130457-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9853389. Licensed CC0.

---

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