# Master Regulatory MicroRNAs in Glioblastoma

> **NIH NIH U01** · UNIVERSITY OF VIRGINIA · 2021 · $67,926

## Abstract

ABSTRACT
Glioblastoma (GBM) is the most common and most deadly primary malignant brain tumor. Despite the most
advanced treatment with combinations of surgery, radiotherapy and chemotherapy, GBM is associated with a
median life expectancy of only ~15 months. Targeted molecular therapies are arguably one of the most
promising approaches to achieving more effective future GBM therapies. A major challenge facing such an
approach is the simultaneous deregulation of multiple molecules in any given single tumor, as demonstrated by
The Cancer Genome Atlas (TCGA) and other published research. Because of this co-deregulation, it is not
surprising that molecular monotherapies have failed to achieve significant improvements in GBM clinical
outcomes. Several lines of evidence suggest that the simultaneous targeting of multiple deregulated molecules
and pathways is required to achieve better therapies. Based on preliminary evidence, we hypothesize that
there exist “master regulatory microRNAs” (miRNAs) that simultaneously regulate multiple
deregulated molecules in GBM. The goal of this application is to discover, investigate, and
therapeutically exploit such miRNAs. We believe that studying them will provide new information on the
mechanisms of gene expression (de)regulation in GBM and that restoring or inhibiting them can be exploited
for therapy. We propose three specific aims. In aim 1, we will use a novel screening approach, PAR-CLIP, in
combination with smRNA-seq and TCGA gene expression data analysis to uncover global miRNA targets and
identify single miRNAs (designated master regulatory miRNAs) that simultaneously target and regulate the
largest number of deregulated molecules in GBM. In aim 2, we will investigate the functions and modes of
action of these master regulatory miRNAs and validate their expressions and targets in human GBM
specimens. In aim 3, we will test miRNAs as novel experimental therapeutic agents or targets in GBM.
Thereby, we will develop and use novel potentially clinically applicable local and systemic delivery agents and
approaches including brain penetrating nanoparticles (BPN), convection-enhanced delivery (CED) and focused
ultrasound with microbubbles (FUS-MB). Successful completion of the proposed studies would establish the
first compendium of miRNA targets in GBM, generate new knowledge on the (de)regulation of gene
expression by miRNAs and their effects on GBM malignancy, and develop novel technologies for the
exploitation of novel master regulatory miRNAs in GBM therapy.

## Key facts

- **NIH application ID:** 10411430
- **Project number:** 3U01CA220841-05S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Roger Abounader
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $67,926
- **Award type:** 3
- **Project period:** 2017-08-09 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411430

## Citation

> US National Institutes of Health, RePORTER application 10411430, Master Regulatory MicroRNAs in Glioblastoma (3U01CA220841-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10411430. Licensed CC0.

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