# The role of RAMS11 in colorectal cancer progression and treatment resistance

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $558,058

## Abstract

PROJECT SUMMARY/ABSTRACT
Although early stage colorectal cancer (CRC) is curable with surgery, there is a critical need to stratify high-risk
early stage patients that would benefit from adjuvant treatment. In contrast to early stage CRC, late-stage
metastatic CRC (mCRC) is usually lethal presenting a critical need to match treatment modalities to patients
based on molecular phenotyping. To address these unmet clinical needs the proposed study aims to
understand the molecular mechanisms enabling primary CRCs to metastasize with the longer-term goal of
rationally guiding treatment decisions. While transcriptome sequencing has provided an unbiased method for
discovering lncRNAs, existing large-scale sequencing projects are comprised of predominantly primary tumors
without matched metastatic samples. This represents a critical barrier to studying lncRNAs involved in the
progression of primary to metastatic disease. To address this gap, we conducted the first meta-analysis of
normal, primary, and distant metastatic tissues across CRC patients to identify differentially expressed RNAs
Associated with Metastasis (RAMS). We prioritized a previously uncharacterized nuclear localized lncRNA,
RAMS11, since: (1) its expression correlated with metastatic progression, (2) its expression associated with
poor disease-free survival across multiple independent patient cohorts, and (3) it promoted oncogenic
phenotypes in vitro and in vivo. Further, subsequent mechanistic experiments demonstrated RAMS11-
dependent recruitment of Chromobox protein 4 (CBX4) to transcriptionally activate Topoisomerase II alpha
(TOP2α). This provides a strong rationale for our hypothesis that RAMS11 interacts with CBX4 to
epigenetically regulate genes to promote oncogenic phenotypes and treatment resistance. This study will focus
on dissecting how RAMS11 dependent CBX4 target gene regulation confers oncogenic phenotypes in vitro
and in vivo. We will also assess whether RAMS11 can help identify high-risk CRC patients and its role in
chemotherapy resistance. Overall, our proposal will significantly advance the lncRNA tumor biology field by
providing mechanistic insight into RAMS11 epigenetic regulation to promote mCRC. Our research has
translational impact by evaluating the potential role of RAMS11 to stratify CRC patients at high-risk of develop
recurrent/metastatic disease that would benefit from specific adjuvant therapies.

## Key facts

- **NIH application ID:** 10467047
- **Project number:** 5R01CA251539-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ryan C Fields
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $558,058
- **Award type:** 5
- **Project period:** 2021-08-10 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467047

## Citation

> US National Institutes of Health, RePORTER application 10467047, The role of RAMS11 in colorectal cancer progression and treatment resistance (5R01CA251539-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10467047. Licensed CC0.

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