# m6A modification of fusion gene mRNAs

> **NIH NIH R03** · UNIVERSITY OF MINNESOTA · 2020 · $77,000

## Abstract

Project Summary
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, accounting for 7% of all pediatric
cancers. Despite extensive studies on the pathogenesis and therapy, the five-year survival rate of 50-70% has
not been improved in the past four decades. In particular, the alveolar type is resistant to all current therapies.
This type is typically characterized by the chromosomal translocations generating the fusion oncogenes PAX3-
FOXO1 and PAX7-FOXO1. These fusion genes contribute to the formation of the sarcoma with a support by
other oncogenes. The PI’s group recently found that the PAX3-FOXO1 mRNA is modified by N6-
methyladenosine (m6A). m6A is the most abundant internal modification in eukaryotic mRNA and long noncoding
RNAs. m6A controls almost all types of RNA metabolism, including alternative splicing, nuclear export, stability,
and translation. Reflecting this diversity, m6A is involved in cancer cell proliferation, metabolism, invasion, and
metastasis. Preliminary studies indicated that PAX3-FOXO1 promotes proliferation of rhabdomyosarcoma cells
and that m6A modification of the PAX3-FOXO1 mRNA is necessary to sustain rapid proliferation of the cells. In
addition, the m6A modification increases the protein level of the fusion gene. Based on these findings, the PI
hypothesized that m6A in the fusion mRNA is a novel regulatory mechanism for alveolar rhabdomyosarcoma
proliferation. This will be tested with the following three aims. In Aim 1, the m6A modification sites within the
PAX3-FOXO1 mRNA will be determined at a single nucleotide level. The information will be used for the
mutagenesis of the modification sites. Aim 2 will study how m6A regulates stability, nuclear export, and translation
of the fusion mRNA. Aim 3 will investigate how m6A of the fusion gene controls proliferation of
rhabdomyosarcoma cells in vitro and in vivo. Collectively, these studies are expected to demonstrate a novel
regulatory mechanism of the fusion mRNA and contribute to the development of novel therapeutic options for
the highly intractable cancer.

## Key facts

- **NIH application ID:** 9968627
- **Project number:** 1R03CA249558-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Nobuaki Kikyo
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,000
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968627

## Citation

> US National Institutes of Health, RePORTER application 9968627, m6A modification of fusion gene mRNAs (1R03CA249558-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968627. Licensed CC0.

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