22: The Long non-coding RNA RAMS11 Promotes Chemotherapy Resistance in-vivo in Metastatic Colorectal Cancer.

Thursday, March 23, 2023

10:26 AM – 10:36 AM

Location: Ballroom C

Abstract Presenter(s)

Abimbola Oyedeji, MD (he/him/his)

Post-Doctoral Research Associate
Washington University in St. Louis
St. Louis, Missouri, United States

Disclosure(s): No financial relationships to disclose

First Author(s)

YK

Yesol Kim, Ph.D

Post-Doctoral Research Associate
Washington University in St. Louis, United States

Disclosure(s): No financial relationships to disclose

Author(s)

NW

Nicole White, Ph.D

Assistant Professor
Washington University in St. Louis, United States

Disclosure information not submitted.
CM

Christopher Maher, Ph.D

Associate Professor
Washington University in St. Louis, United States

Disclosure information not submitted.
JM

Jacqueline Mudd, B.Sc.

Staff Scientist
Washington University in St. Louis, United States

Disclosure information not submitted.
DS

Duanwen Shen, Ph.D

Senior Scientist
Washington University in St. Louis, United States

Disclosure information not submitted.
PG

Peter Goedegebuure, PhD

Associate Professor
Washington University in St. Louis, Department of Surgery, St. Louis, MO, United States

Disclosure information not submitted.
Ryan C. Fields, MD

Chief, Surgical Oncology; Professor of Surgery
Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center at Washington University School of Medicine
St.Louis, MO, United States

Disclosure information not submitted.

Disclosure(s):

Abimbola Oyedeji, MD.: No financial relationships to disclose

Yesol Kim, Ph.D: No financial relationships to disclose

Introduction: While there are several therapeutic treatment options available for patients with metastatic colon cancer (mCRC), there are few pre-treatment data that can predict the response to treatment and development of resistance. We have previously shown that the long non-coding RNA (lncRNA), RAMS11, promotes the progression of mCRC. Based on mechanistic data, we hypothesized that high expression of RAMS11 would be associated with resistance to 5-FU based chemotherapy in mCRC.

Methods: 9-week-old female NOD SCID mice were injected with 1e6 wild type (WT) or RAMS11- overexpressing (RAMS11-OE) human CRC, HT29 cells (expressing GFP-luciferase ) via the tail vein; a common model for establishment of lung metastases . 72 hours after tumor cell injection, mice were subcutaneously treated with vehicle (PBS) or 50mg/kg 5FU. Mice were imaged weekly by bioluminescence to monitor tumor growth.

Results: Analysis of viable tumor cells by bioluminescence imaging (BLI) showed a significant increase in lung metastases in RAMS11-OE tumor-bearing mice compared to WT tumor-bearing mice (Fig. 1). WT tumor-injected mice treated with 5FU showed a 37% - 67% reduction of tumor burden over the 3-week time course (Fig. 1A, B). Ex vivo BLI analysis of lung tissue showed a 55% decrease at Week 3 (p < 0.05, Fig. 1C, D). However, there was no significant change in tumor size in vehicle and 5FU-treated mice with RAMS11-OE tumors by both in vivo and ex vivo lung analysis using BLI.

Conclusions: High expression of RAMS11 promotes resistance to 5-FU chemotherapy in HT29 mCRC. RAMS11 status may represent a novel pre-treatment diagnostic to predict response to chemotherapy and identify aggressive tumor biology in patients with mCRC.

Learning Objectives:

Recognize the potential importance of pre-treatment diagnostic determination of RAMS11 status
Understand the impact of lncRNA on tumor biology and progression.
Recognize the need to identify other relevant ways to predict the response to treatment and development of resistance in metastatic colorectal cancer