# Understanding the regulatory role and therapeutic potential of long non-coding RNAs in metastatic colorectal cancer

> **NIH NIH K22** · WASHINGTON UNIVERSITY · 2022 · $189,462

## Abstract

Project Summary/Abstract
The overall research goal of this proposal is to elucidate the mechanisms driving mCRC to better assess
the critical need for discovery of biomarkers and targeted therapies. Although early stage colorectal
cancer (CRC) is curable with surgery and adjuvant therapy, metastatic CRC (mCRC) is usually lethal. Despite
advances in our understanding of primary CRC oncogenesis, the mechanisms by which CRC becomes
metastatic and leads to patient death is poorly characterized. In addition, the lack of reliable biomarkers to
predict development of mCRC and select patients for further treatment is a critical barrier. To address this
critical knowledge gap, our proposal seeks to understand how long non-coding RNAs (lncRNAs) enable
primary tumors to invade and metastasize to develop improved diagnostics and therapeutics. Therefore, we
performed transcriptome analysis of 37 patient matched normal, primary, and distant metastatic colorectal
cancer tissues to discover 148 differentially expressed (DE) RNA Associated with Metastasis (RAMS). Notably,
the top up-regulated novel candidate, RAMS11, (i) is associated with poor survival, (ii) induces invasion in vitro
and in vivo, (ii) increases resistance to topoisomerase inhibitors, (iii) interacts with chromobox homology 4
(CBX4), and (iv) and can be targeted with locked nucleic acids in vitro. This serves as the rationale for our
hypothesis that RAMS11 may serve as a prognostic biomarker associated with poor outcome by interacting
with CBX4 to epigenetically regulate genes and can be therapeutically targeted in mCRC. To demonstrate this,
Aim 1 will evaluate RAMS11 as a prognostic biomarker associated with poor long-term outcome. Aim 2 will
characterize RAMS11-dependant CBX4 regulation. Lastly, Aim 3 will evaluate RAMS11 therapeutic potential.
This proposal will establish the importance of RAMS11 as a master epigenetic regulator to promote colon
cancer metastasis. Furthermore, this research is of translational impact by evaluating the prognostic and
therapeutic potential of targeting RAMS11 directly with locked nucleic acid antisense oligonucleotides.

## Key facts

- **NIH application ID:** 10437635
- **Project number:** 5K22CA241329-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jessica Silva-Fisher
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $189,462
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437635

## Citation

> US National Institutes of Health, RePORTER application 10437635, Understanding the regulatory role and therapeutic potential of long non-coding RNAs in metastatic colorectal cancer (5K22CA241329-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437635. Licensed CC0.

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