# Role of METTL3 and the m6A Epitranscriptome in cancer

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $649,539

## Abstract

Lung adenocarcinoma accounts for about 40% of all lung cancers and is the most common form of lung
cancer found in women and in people under the age of forty-five. Strikingly, the 5-year survival rate for lung
cancer overall is only about 18 percent, and more than half of people with lung cancer die within one year of
diagnosis. This highlights the need for more effective treatment options and underscores the importance of
research focused on uncovering and understanding new molecular and cellular pathways that contribute to
lung cancer biology. Messenger RNAs (mRNAs) are subject to various posttranscriptional modifications
including N6-Methyladenosine (m6A). m6A is the most abundant mRNA modification and is emerging as an
important regulator of gene expression that can affect mRNA splicing, export, stability, and translation. m6A
is catalyzed the METTL3 methyltransferase complex, and occurs at a characteristic sequence motif at a
position close to the translation stop codon of a large subset of mRNAs. The goal of this proposal is to test
the central hypothesis that METTL3 is a novel oncogenic factor in lung cancer. The global m6A mRNA
`epitranscriptome' will be mapped and measured in a cohort of primary human lung tumor samples. Relative
levels of METTL3 in tumors will be measured by immunohistochemistry and correlated with the m6A levels
and transcriptome-wide distribution. Loss- and gain-of-function experiments will address the widespread
impact of METTL3 (and METTL3-interacting proteins) in controlling target mRNA expression, and will help
uncover the molecular and cellular role of METTL3, METTL3-interacting proteins, and a selection of
downstream targets mRNAs, in lung cancer cell biology. Finally, the effects of METTL3 manipulation in lung
tumor initiation and progression will be explored using a mouse lung cancer model, as well as a novel lung
organoid model and a panel of assays will be deployed to examine the underlying molecular mechanism.
Successful completion of the proposed studies will help establish METTL3 as a possible future therapeutic
target for lung adenocarcinoma and other cancers.

## Key facts

- **NIH application ID:** 10070087
- **Project number:** 5R01CA233671-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Richard I. Gregory
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $649,539
- **Award type:** 5
- **Project period:** 2019-12-11 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070087

## Citation

> US National Institutes of Health, RePORTER application 10070087, Role of METTL3 and the m6A Epitranscriptome in cancer (5R01CA233671-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10070087. Licensed CC0.

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