# MiR-17 mediates sulindac anti-metastatic activity in human colorectal cancer

> **NIH VA I01** · SOUTHEAST LOUISIANA VETERANS HEALTH CARE · 2022 · —

## Abstract

PROJECT SUMMARY:
In the United States, approximately 3% of cancer patients are being treated in the Veterans Affairs Medical
Centers (VAMCs) each year, of which 11% are colon or rectal malignancies. Colorectal cancer (CRC) remains
a leading cause of cancer-related death in the United States. Although the overall survival for CRC patients with
advanced disease has been dramatically improved over the past decades, the most recently reported 5-year
survival rate for patients with stage IV CRC was lower than 14%. To date, there are only a few drugs approved
by the FDA to treat CRC patients with advanced disease. Along with new military personnel entering the VA
system, physician shortages, and extended lifespan of seniors, the demands on VA health care resources are
becoming significant. Therefore, developing more efficacious and safer therapeutics for treating veteran patients
could be an economical and feasible strategy to offset the pressure on the VAMCs due to the increasing needs
for VA health care.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to significantly reduce the incidence and risk
of death from CRC and other forms of cancer. Sulindac, in particular, has been shown to display strong efficacy
for the treatment of precancerous lesions in patients with familial adenomatous polyposis by reducing the size
and number of polyps as much as 60-70%. These observations are consistent with numerous preclinical studies
that have shown the ability of sulindac and other NSAIDs to inhibit tumorigenesis in various experimental animal
models involving either early or late-stage diseases. However, the cardiovascular toxicity associated with
cyclooxygenase/prostaglandin (COX/PGE) inhibition precludes the long-term use of NSAIDs for cancer
indications in the general population. Our preliminary studies support a novel notion that a low dose of sulindac
inhibits CRC cell invasion and metastasis with non-COX/PGE inhibition mechanisms involving select miRNAs.
Of interest, exosomal miR-17-5p (ES-miR-17-5p), for the first time, was found to act as one of the key mediators
targeted and modulated by sulindac to intervene in pre-metastatic niche formation. These data provide an
innovative insight into the potential of utilizing low dose sulindac to prevent and block CRC metastatic
progression, which has not yet been studied exclusively. We hypothesize that ES-miR-17-5p is intimately
involved in the molecular mechanism by which low dose sulindac can delay and potentially block CRC distant
metastasis. Three specific aims are proposed in pursuit of our premise to demonstrate a new indication of low
dose sulindac in control of metastatic CRC. In Aim 1, we will study a new mechanism involving ES-miR-17-5p
in order to understand the inhibitory activity of sulindac in CRC cell motility; in Aim 2, we will determine the role
of ES-miR-17-5p in mediating the in vivo anti-metastatic activity of sulindac utilizing animal models; in Aim 3, we
will evaluate the cl...

## Key facts

- **NIH application ID:** 10258119
- **Project number:** 1I01BX005094-01A2
- **Recipient organization:** SOUTHEAST LOUISIANA VETERANS HEALTH CARE
- **Principal Investigator:** Yaguang Xi
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-09-30 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10258119

## Citation

> US National Institutes of Health, RePORTER application 10258119, MiR-17 mediates sulindac anti-metastatic activity in human colorectal cancer (1I01BX005094-01A2). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10258119. Licensed CC0.

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