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Novel positioning from obesity to cancer: FTO, an m6A RNA demethylase, regulates tumour progression

  • JiaLing Chen
  • Bin DuEmail author
Review – Cancer Research
  • 410 Downloads

Abstract

Purpose

The fat mass- and obesity-associated (FTO) gene on chromosome 16q12.2 shows an intimate association with obesity and body mass index. Recently, research into the FTO gene and its expression product has attracted widespread interest due to the identification of FTO as an N6-methyladenosine (m6A) demethylase. FTO primarily regulates the m6A levels of downstream targets via their 3′ untranslated regions. FTO not only plays a critical role in obesity-related diseases but also is involved in the occurrence, development and prognosis of many types of cancer, such as acute myeloid leukaemia, glioblastoma and breast cancer. Currently, studies indicate that FTO is a crucial component of m6A modification, it regulates cancer stem cell function, and promotes the growth, self-renewal and metastasis of cancer cells. In this review, we summarized and analysed the data regarding the structural features and biological functions of FTO as well as its association with different cancers and possible molecular mechanisms.

Methods

We systematically reviewed the related literatures regarding FTO and its demethylation activity in many pathologic and physiological processes, especially in cancer-related diseases based on PubMed databases in this article.

Results

Mounting evidence indicated that FTO plays a critical role in occurrence, progression and treatment of various cancers, even acting as a cancer oncogene in acute myeloid leukaemia, research on which is no longer restricted to metabolic diseases such as obesity and diabetes.

Conclusion

Considering FTO’s critical role in many diseases, FTO may become a new promising target for the diagnosis and treatment of various diseases in the near future, especially for specific types of cancers, such as acute myeloid leukaemia, glioblastoma and breast cancer.

Keywords

FTO M6A RNA demethylase Tumourigenesis Oncogene Proliferation Chemo-radiotherapy resistance 

Abbreviations

FTO

Fat mass and obesity-associated

BMI

Body mass index

T2DM

Type 2 diabetes mellitus

SNPs

Single-nucleotide polymorphisms

m6A

N6-methyladenosine

GWAS

Genome-wide association studies

XPO2

Exportin 2

UTRs

Untranslated regions

2-OG

2-oxoglutarate

3-meT

3-methylthymidine

AML

Acute myeloid leukaemia

MLL

Mixed lineage leukaemia

3-meU

3-methyluracil

CSC

Cancer stem cell

DNMT

DNA methyltransferases

IRX3

Iroquois-related homeobox 3

circRNAs

Circular RNAs

mRNAs

Messenger RNAs

lncRNAs

Long non-coding RNAs

METTL14

Methyltransferase-like 14

METTL3

Methyltransferase-like 3

WTAP

Wilms’ tumour 1-associating protein

ALKBH5

AlkB homologue 5

ASB2

Ankyrin-repeat SOCS box-containing protein 2

RARA

Retinoic acid receptor alpha

ATRA

All-trans-retinoic acid

R-2HG

R-2-hydroxyglutarate

IDH1/2

Isocitrate dehydrogenase ½

CEBPA

CCAAT enhancer-binding protein alpha

GSCs

Glioblastoma stem cells

FOXM1

Forkhead box transcription factor M1

ERCC1

Excision repair cross-complementation group 1

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation of China (China; 31201028, 81872893), the Fundamental Research Fund for the Central Universities (China; 21617462), the Guangzhou Science Technology and Innovation Commission (China; 201707010099), the Medical Scientific Research Foundation of Guangdong Province (China; A2017574) and the Provincial Undergraduates’ Innovation and Entrepreneurship Training Programs (China; 82618257).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologySchool of Medicine, Jinan UniversityGuangzhouChina

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