Biomarker: FTO

Biomarker subtype: mRNA

Clinical application: treatment(theranostic target)

Histology type: endometrial carcinoma

Sample type : tissue

Clinical method: Quantitative real-time PCR

Expression pattern : FTO demethylates m6A modifications

Validation in cell line : cell lines (AN3CA and KLE)

Validation in cell method : Subcellular fractionation analysis,Western blotting (WB),Lentivirus construction and infection, plasmid and siRNA transfection,Inhibition of the WNT signalling pathway,Wound-healing assays,Transwell assay,RIP-seq and RIP-qPCR,Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and quantitative PCR (MeRIP-PCR),RNA sequencing (RNA-seq) and quantitative PCR (qPCR),RNA pull-down assays,Luciferase reporter assays,RNA half-life assays,

Validation involved pathway : WNT signalling pathway

Description: We found that the expression of FTO can promote the metastasis of EC. Mechanistically, FTO removed the m6A modification from HOXB13 mRNA and abolished the YTHDF2-mediated degradation of HOXB13, promoting HOXB13 protein expression and activates the WNT signalling pathway, and promotes EC invasion and metastasis

Funtion description: High expression of FTO in metastatic EC and that this action promote both metastasis and invasion in vivo and in vitro.FTO can catalyse demethylation modification in 3?UTR region of HOXB13 mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein. Decreasing HOXB13 mRNA decay and increasing HOXB13 protein expression was accompanied by WNT signalling pathway activation and the expression of downstream proteins, leading to tumour metastasis and invasion. The WNT signalling pathway inhibitor ICG-001 can block HOXB13 gene-induced tumour metastasis, therefore ICG-001 may be a promising molecular intervention.

Approved symbol: FTO

Approved name: FTO alpha-ketoglutarate dependent dioxygenase

Locus type: gene with protein product

HGNC ID: HGNC:24678

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24678

Symbol status: Approved

Alias symbols: KIAA1752 MGC5149 ALKBH9

OMIM: 610966

Omim link: https://www.omim.org/entry/610966

NCBI name: 79068

NCBI link: https://www.ncbi.nlm.nih.gov/gene/79068

Summary: This gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]

Expression: Ubiquitous expression in brain (RPKM 7.3), adrenal (RPKM 4.2) and 25 other tissues

NCBI gene expression https://www.ncbi.nlm.nih.gov/gene/79068#gene-expression

PDB ID: Q9C0B1

PDB link: https://www.ebi.ac.uk/pdbe/entry/search/index/?searchParams=%7B%22q_uniprot%22:%5B%7B%22value%22:%22(Q9C0B1)%22,%22condition1%22:%22AND%22,%22condition2%22:%22Contains%22%7D%5D,%22resultState%22:%7B%22tabIndex%22:0,%22paginationIndex%22:1,%22perPage%22:%2210%22,%22sortBy%22:%22Sort%20by%22%7D%7D

MF term ID: GO:1990931$GO:1990984

MF term name: mRNA N6-methyladenosine dioxygenase activity$tRNA demethylase activity

Source description: WP

Term ID: WP:WP3407

Term name: FTO obesity variant mechanism