# Role of long non-coding RNAs in sarcoma pathogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $393,107

## Abstract

PROJECT SUMMARY
Ewing sarcoma is a rare tumor that occurs in children and young adults. The driving oncogenic event in this
disease is most commonly the translocation EWS/FLI. Similar translocations involving ETS transcription
factors occur in other malignancies, including prostate cancer, broadening the potential relevance of our
studies. Prior work has determined that EWS/FLI can lead to chromatin reprogramming by repressing some
enhancers while activating others through direct binding. Our own data indicates that EWS/FLI also
upregulates expression of lncRNAs. The primary goal of this proposal is to elucidate the molecular function of
lncRNAs in Ewing sarcoma. Our preliminary data indicates that two lncRNAs, EWSAT1 and EWSAT2, may be
involved in the oncogenic effects of Ewing sarcoma. Knock-down of either of these RNAs strongly decreases
proliferation of Ewing tumors in vitro and in vivo. Furthermore, RNAseq analysis indicates that both of these
lncRNAs repress a significant number of genes also known to be repressed by EWS/FLI. Our primary goal in
this proposal is to elucidate the molecular function through which these lncRNAs act to promote Ewing
sarcoma. We will focus our studies on determining how these lncRNAs lead to transcriptional repression.
In Aim 1, we will elucidate define how expression of EWSAT1 and 2 alters key protein-protein interactions in
Ewing cells. Specifically, we will test the hypothesis that EWSAT1 or 2 expression alters PPIs for EWS/FLI,
EWS or hnRNPK. In Aim 2, we will test the hypothesis that EWSAT1 or 2 function by modulating the ability of
EWS/FLI to bind to specific enhancers. ChIPseq and ChIRPseq will be used to determine how these lncRNAs
interact with chromatin and how they alter binding of histones and other chromatin regulators. In Aim 3, we will
elucidate the functional consequences of EWSAT1/2 loss or overexpression using Ewing patient derived
xenografts and cell lines.

## Key facts

- **NIH application ID:** 10114979
- **Project number:** 5R01CA211657-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Eric Alejandro Sweet-Cordero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $393,107
- **Award type:** 5
- **Project period:** 2017-03-13 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114979

## Citation

> US National Institutes of Health, RePORTER application 10114979, Role of long non-coding RNAs in sarcoma pathogenesis (5R01CA211657-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114979. Licensed CC0.

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