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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | Epigenetics | Research

METTL3-mediated m6A mRNA modification of FBXW7 suppresses lung adenocarcinoma

Authors: Yingtong Wu, Ning Chang, Yong Zhang, Xinxin Zhang, Leidi Xu, Yinggang Che, Tianyun Qiao, Bin Wu, Ying Zhou, Jun Jiang, Jie Xiong, Jian Zhang, Jian Zhang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

Background

FBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear.

Methods

The correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development.

Results

Decreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored LUAD cell suppression in vitro and in vivo.

Conclusions

Our findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.
Appendix
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Metadata
Title
METTL3-mediated m6A mRNA modification of FBXW7 suppresses lung adenocarcinoma
Authors
Yingtong Wu
Ning Chang
Yong Zhang
Xinxin Zhang
Leidi Xu
Yinggang Che
Tianyun Qiao
Bin Wu
Ying Zhou
Jun Jiang
Jie Xiong
Jian Zhang
Jian Zhang
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Epigenetics
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-021-01880-3

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