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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Breast Cancer | Research

RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3

Authors: Yi Niu, Ziyou Lin, Arabella Wan, Honglei Chen, Heng Liang, Lei Sun, Yuan Wang, Xi Li, Xiao-feng Xiong, Bo Wei, Xiaobin Wu, Guohui Wan

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Background

N6-methyladenosine (m6A) modification is the most pervasive modification in mRNA, and has been considered as a new layer of epigenetic regulation on mRNA processing, stability and translation. Despite its functional significance in various physiological processes, the role of the m6A modification involved in breast cancer is yet fully understood.

Methods

We used the m6A-RNA immunoprecipitation sequencing to identify the potential targets in breast cancer. To determine the underlying mechanism for the axis of FTO-BNIP3, we performed a series of in vitro and in vivo assays in 3 breast cancer cell lines and 36 primary breast tumor tissues and 12 adjunct tissues.

Results

We showed that FTO, a key m6A demethylase, was up-regulated in human breast cancer. High level of FTO was significantly associated with lower survival rates in patients with breast cancer. FTO promoted breast cancer cell proliferation, colony formation and metastasis in vitro and in vivo. We identified BNIP3, a pro-apoptosis gene, as a downstream target of FTO-mediated m6A modification. Epigenetically, FTO mediated m6A demethylation in the 3’UTR of BNIP3 mRNA and induced its degradation via an YTHDF2 independent mechanism. BNIP3 acts as a tumor suppressor and is negatively correlated with FTO expression in clinical breast cancer patients. BNIP3 dramatically alleviated FTO-dependent tumor growth retardation and metastasis.

Conclusions

Our findings demonstrate the functional significance of the m6A modification in breast cancer, and suggest that FTO may serve as a novel potential therapeutic target for breast cancer.
Appendix
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Metadata
Title
RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3
Authors
Yi Niu
Ziyou Lin
Arabella Wan
Honglei Chen
Heng Liang
Lei Sun
Yuan Wang
Xi Li
Xiao-feng Xiong
Bo Wei
Xiaobin Wu
Guohui Wan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1004-4

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