# Transcribed Ultra Conserved Regions in Glioblastoma

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2022 · $201,875

## Abstract

ABSTRACT
Glioblastoma (GBM) is the most common and deadliest primary malignant brain tumor. Most GBM research has
focused on protein-coding genes and less on non-coding transcripts that make up 98% of cellular RNA.
Transcribed Ultra-Conserved Regions (TUCRs) are a group of 481 transcripts that are 100% conserved across
multiple species. They are highly resistant to variation and are commonly deregulated in cancer, suggesting
regulatory and functional importance. Some evidence suggests that most TUCRs are long non-coding RNAs
(lncRNAs) that are highly conserved, unlike most other lncRNAs that are usually poorly conserved. TUCRs are
largely understudied in cancer and not at all in GBM. As of the date of submission of this R21 application, there
were no published studies on TUCRs in GBM. In preliminary work, we performed the first analysis of TUCR
expression in GBM using The Cancer Genome Atlas (TCGA) RNA-Seq data and identified 194 TUCRs that are
differentially expressed relative to normal brain. Many of these TUCRs correlated with patient survival. This
project aims to identify and characterize TUCRs that are differentially expressed in GBM and to uncover their
functions and mechanisms of action. We propose three specific aims. In Aim 1, we will identify and
characterize TUCRs that are differentially expressed in GBM. Candidate TUCRs will be identified from
TCGA RNA-Seq data analyses and prioritized based on their differential expression and correlation with survival.
Their full transcript sequences will be uncovered and their lncRNA status verified. In Aim 2, we will uncover
the functions of select TUCR lncRNAs in GBM. The top 20 ranked TUCR lncRNAs from aim 1 will be used
for this aim. TUCR lncRNAs will be overexpressed and knocked down/out in GBM cell lines and stem cells. The
effects of the TUCRs on cell proliferation, survival, invasion, migration and stem cell differentiation as well as on
in vivo tumor growth in an RCAS/Tva immune competent mouse model of GBM will be analyzed. In Aim 3, we
will identify the mechanism of action for select TUCR lncRNAs in GBM. TUCRs that exert regulatory effects
on GBM malignancy as determined in aim 2 will be prioritized. We will identify the subcellular localization of each
TUCR lncRNA and use a multipronged approach consisting of bioinformatics and experimental determination of
protein and nucleic acid binding partners followed by functional rescue experiments to uncover the mechanisms
of action of TUCR lncRNAs. Successful completion of this project would represent the first comprehensive
analysis of TUCRs in GBM and generate new knowledge on the mechanisms of GBM malignancy.

## Key facts

- **NIH application ID:** 10377434
- **Project number:** 5R21NS122136-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Roger Abounader
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377434

## Citation

> US National Institutes of Health, RePORTER application 10377434, Transcribed Ultra Conserved Regions in Glioblastoma (5R21NS122136-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10377434. Licensed CC0.

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