86: Targeting Small Non-coding RNAs to Treat Dedifferentiated Liposarcoma

Thursday, March 21, 2024

11:16am – 11:26am ET

Location: C105-C106

Abstract Presenter(s)

Elizaveta K. Titerina, MD

Post Doctoral Scholar
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University
COLUMBUS, Ohio, United States

Submitter(s)

Elizaveta K. Titerina, MD

Post Doctoral Scholar
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University
COLUMBUS, Ohio, United States

Author(s)

Elizaveta K. Titerina, MD

Post Doctoral Scholar
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University
COLUMBUS, Ohio, United States
MG

Marina Goryunova, MD

Post Doctoral Scholar
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, United States
NS

Nipin Sp, PhD

Post Doctoral Scholar
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, United States
CK

Carson Karakis, n/a

Student Assistant
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, United States
PS

Patricia Sarchet, PhD

Researcher
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, United States
RP

Raphael E. Pollock, MD, PhD

Professor
Department of Surgery, Division of Surgical Oncology, The James Comprehensive Cancer Center, The Ohio State University, United States
CC

Carlo M. Croce, MD

Professor
Department of Cancer Biology and Genetics, The James Comprehensive Cancer Center, The Ohio State University, United States
AL

Alessandro La Ferlita, PhD

Post Doctoral Scholar
Department of Cancer Biology and Genetics, The James Comprehensive Cancer Center, The Ohio State University, United States
JB

Joal D. Beane, MD

Assistant Professor of Surgery
The Ohio State University
Columbus, Ohio, United States

Disclosure(s):

Elizaveta K. Titerina, MD: No financial relationships to disclose

Introduction: Dedifferentiated liposarcoma (ddLPS) is associated with a poor prognosis, with a five-year survival rate of up to 30%. Currently, the only curative treatment for ddLPS is surgical resection. Chemotherapy is the standard of care for advanced ddLPS, with a response rate of less than 25%. Small non-coding RNAs (sncRNAs) are a diverse group of regulatory RNAs that play a key role in many biological processes, like cell growth, differentiation, and apoptosis. The aim of this study was to identify and characterize the role of dysregulated sncRNAs in ddLPS.

Methods: We sequenced small RNAs on 12 primary human ddLPS samples and 9 normal adjacent fat tissues. Raw counts were scaled in reads per million to filter out low-expressed sncRNAs. Afterward, raw counts of retained sncRNAs were log2-transformed, and differential expression analysis was performed by the Limma R package. SncRNAs with a |Log2FC| >0.58 and an adjusted P.val < 0.05 were considered dysregulated. Survival analysis on ddLPS cohort retrieved from TCGA (n=58) was carried out by the Survival R package. In vitro inhibition of miR-138-5p and transwell migration assay performed in ddLPS Lipo863 cell line.

Results: Compared to normal adjacent fat, we identified 111 upregulated and 150 downregulated sncRNAs in ddLPS, including microRNAs (miRNAs) and tRNA-derived sncRNAs (tsRNAs). One of the sncRNAs exhibiting pronounced upregulation was miR-138-5p. Importantly, there was a significant association (P.val = 0.0014) between high expression of miR-138-5p (over the median) and poorer overall survival. Upregulation of miR-138-5p was confirmed in the ddLPS cell line, Lipo863. Inhibition of miR-138-5p significantly decreased migration in Lipo863 cells. In addition to miRNAs, we found multiple tsRNAs, a relatively understudied class of sncRNAs, that were dysregulated in ddLPS, including a notable downregulation of ts-47. Further research is needed to elucidate the functional role of tsRNAs in ddLPS and their potential as therapeutic targets.

Conclusions: Dysregulation of sncRNAs represents an unexplored layer of ddLPS tumor biology that is important for cell migration. The development of effective strategies to target sncRNAs like miR-138-5p may lead to novel and more effective treatments for patients with ddLPS.

Learning Objectives:

Discuss new strategies to treat dedifferentiated liposarcoma.
Improve their knowledge of the role of small non-coding RNAs in dedifferentiated liposarcoma.
Unveil the role of small non-coding RNAs in the pathogenesis of dedifferentiated liposarcoma and the way of using this knowledge for developing new treatment strategies.