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

  • Review – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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.

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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

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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).

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  1. Department of Pathology, School of Medicine, Jinan University, Guangzhou, China

    JiaLing Chen & Bin Du

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  1. JiaLing Chen
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Correspondence to Bin Du.

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Chen, J., Du, B. Novel positioning from obesity to cancer: FTO, an m6A RNA demethylase, regulates tumour progression. J Cancer Res Clin Oncol 145, 19–29 (2019). https://doi.org/10.1007/s00432-018-2796-0

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