# Role of m6A RNA methylation in Regulation of Translation in Human Glioblastoma

> **NIH NIH R21** · RHODE ISLAND HOSPITAL · 2020 · $176,654

## Abstract

Abstract
Glioblastoma represents the most aggressive type of human brain cancer with dismal prognosis. Recent
studies have revealed extensive intratumoral heterogeneity in transcript expression and increased plasticity of
human glioma stem cells, which are thought to contribute to treatment failure and tumor recurrence. The role of
m6A RNA and ALKBH5 in the regulation of self-renewal and maintenance of tumorigenicity of glioma stem cells
has been recently demonstrated. Limited knowledge exists with regards to the role of m6A RNA methylation in
the regulation of translation efficiency in human cancer cells. Moreover, the role of m6A RNA methylation
machinery that includes m6A “writers” (methyltransferases e.g. Mettl14, Mettl3) and “erasers” (demethylases
e.g. ALKBH5, FTO), in the regulation of translation during the transition of human glioma stem cells to
differentiated glioma cells has not been studied.
We hypothesize that alterations at the level of m6A RNA methylation influences the rate of translation of certain
transcripts during the transition of human glioma stem cells to differentiated cells. We propose that loss of m6A
RNA methylation increases the rate of translation of transcripts with sequence motifs of their m6A peak regions
that are complementary to the seed sequences of specific miRNAs. These miRNAs interact and regulate the
m6A RNA machinery in human glioma cells.
The specific aims of our proposal will provide a comprehensive and subtype specific insight into the role of m6A
RNA in the regulation of translation during the transition between hGSCs and differentiated GCs:
-SA1: Perform RNA sequencing, MeRIP sequencing, Ribo-sequencing and computational analysis of 10
additional human glioma stem cells and differentiated glioma cells
-SA2: Determine the functional significance of the miRNA binding within the m6A RNA methylation peaks and
how the miRNAs regulate RNA methylation machinery.
Our proposal constitutes a functional exploration of the role of m6A RNA methylation in the regulation of
translation during the transition of hGSCs to differentiated cells. In addition, it introduces the role of specific
miRNAs as regulators of hGSC translation through modulation of the RNA methylation machinery. Since the
reversible transition of hGSCs to differentiated cells constitutes a critical denominator of tumor recurrence and
aggression, identification of molecular regulators of this process could provide novel targets for therapeutic
interventions.

## Key facts

- **NIH application ID:** 9982242
- **Project number:** 5R21CA235415-02
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** Nikolaos Tapinos
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $176,654
- **Award type:** 5
- **Project period:** 2019-07-23 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982242

## Citation

> US National Institutes of Health, RePORTER application 9982242, Role of m6A RNA methylation in Regulation of Translation in Human Glioblastoma (5R21CA235415-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9982242. Licensed CC0.

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