Abstract | BACKGROUND: METHODS: We investigated the expression of the m6A regulator genes and their prognostic potential in a large clinical cohort of 173 GC patients using qRT-PCR assays. In addition, we undertook a series of in-vitro and in-vivo functional studies to investigate the oncogenic role of FTO. RESULTS: GC patients with low expression of METTL3, METTL14, ALKBH5, WTAP and YTHDF1 demonstrated significantly poor OS, while patients with high FTO expression exhibited markedly worse OS. Furthermore, the cumulative risk-score derived from these gene panel also significantly associated with poor OS, with a corresponding hazard ratio of 5.47 (95% CI: 3.18-9.41, p < 0.0001). We observed that FTO expression was frequently upregulated in GC cell lines, with epithelial-mesenchymal-transition (EMT) features. FTO knockdown in HGC27 and AGS cells inhibited cell proliferation and migratory potential, while its overexpression in MKN28 cells resulted in enhanced proliferation and migration. Finally, confirming our in-vitro findings, FTO suppression led to significant tumour growth inhibition in a HGC27 xenograft model. CONCLUSIONS: We demonstrate that m6A regulators may serve as promising prognostic biomarkers in GC. Our functional studies reveal that FTO is an important oncogene and may be a promising therapeutic target associated with EMT-alterations in gastric cancer.
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Authors | Tadanobu Shimura, Raju Kandimalla, Yoshinaga Okugawa, Masaki Ohi, Yuji Toiyama, Chuan He, Ajay Goel |
Journal | British journal of cancer
(Br J Cancer)
Vol. 126
Issue 2
Pg. 228-237
(02 2022)
ISSN: 1532-1827 [Electronic] England |
PMID | 34675398
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2021. The Author(s), under exclusive licence to Springer Nature Limited. |
Chemical References |
- Biomarkers
- N-methyladenosine
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO
- FTO protein, human
- Adenosine
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Topics |
- Adenosine
(analogs & derivatives, metabolism)
- Adult
- Aged
- Aged, 80 and over
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO
(genetics, metabolism)
- Animals
- Biomarkers
(metabolism)
- Cell Movement
- Cell Proliferation
- DNA Methylation
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Male
- Mice
- Mice, Nude
- Middle Aged
- Prognosis
- ROC Curve
- Stomach Neoplasms
(genetics, metabolism, pathology)
- Survival Rate
- Xenograft Model Antitumor Assays
- Young Adult
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