RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway.

Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE

Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-

Alpha-Ketoglutarate-Dependent Dioxygenase FTO*/metabolism ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO*/genetics ; Stomach Neoplasms*/genetics ; Stomach Neoplasms*/pathology ; Stomach Neoplasms*/metabolism ; Ataxia Telangiectasia Mutated Proteins*/metabolism ; Ataxia Telangiectasia Mutated Proteins*/genetics ; Sp1 Transcription Factor*/metabolism ; Sp1 Transcription Factor*/genetics ; Aurora Kinase B*/metabolism ; Aurora Kinase B*/genetics; Humans ; Cell Line, Tumor ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Middle Aged ; Signal Transduction ; Prognosis ; Mice ; Animals

Gastric cancer (GC) is the 5 ^th most prevalent cancer and the 4 ^th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients' therapy response and prognosis.
(© 2024. The Author(s).)

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EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
EC 1.14.11.33 (FTO protein, human)
EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
0 (Sp1 Transcription Factor)
EC 2.7.11.1 (Aurora Kinase B)
EC 2.7.11.1 (AURKB protein, human)
EC 2.7.11.1 (ATM protein, human)
0 (SP1 protein, human)

Date Created: 20240702 Date Completed: 20240702 Latest Revision: 20240705

20240705

PMC11220007

10.1038/s42003-024-06477-y

38956367