Japan Digestive Disease Week 2022
International Poster Session2 (JDDW)
October 28, 10:18–11:06, Room 15 (Marine Messe Fukuoka Arena Digital Poster Session)
IP-7_S
Novel findings for m6A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer Poster Award Young Award
- 1
- Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine
- 2
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute, Baylor University Medical Center
- 3
- Department of Genomic Medicine, Mie University
Background: While emerging evidence indicates that N6-methyladenosine (m6A) regulators play crucial roles in cancer progression, their oncological and clinical significance in gastric cancer (GC) has not been fully elucidated.
Aim and methods: In this study, we investigated the mRNA expression level of seven m6A regulator genes and their prognostic potential in 173 GC patients. Furthermore, we investigated the oncogenic role of FTO using in a series of in-vitro and in-vivo experimental models.
Results: GC patients with low expression of METTL3, METTL14, ALKBH5, WTAP and YTHDF1 demonstrated significantly poor OS (p＜0.05), while patients with high FTO expression exhibited markedly dismal OS (p＜0.001). Subsequently, we observed that FTO knockdown (KD) in HGC27 and AGS cells inhibited proliferation and migratory potential. Intriguingly, epithelial-mesenchymal-transition (EMT) features were attenuated in the FTO-KD GC cells. On the other hand, FTO-overexpression in MKN28 cells enhanced their aggressive phenotype. Finally, to confirm our in-vitro findings, FTO suppression led to significant tumor growth inhibition in a HGC27 xenograft model.
Conclusion: We demonstrate that m6A regulators may serve as promising prognostic biomarkers in GC. Moreover, our functional studies reveal that FTO possesses oncogenic role and may be a promising therapeutic target associated with EMT-alterations in GC.
Aim and methods: In this study, we investigated the mRNA expression level of seven m6A regulator genes and their prognostic potential in 173 GC patients. Furthermore, we investigated the oncogenic role of FTO using in a series of in-vitro and in-vivo experimental models.
Results: GC patients with low expression of METTL3, METTL14, ALKBH5, WTAP and YTHDF1 demonstrated significantly poor OS (p＜0.05), while patients with high FTO expression exhibited markedly dismal OS (p＜0.001). Subsequently, we observed that FTO knockdown (KD) in HGC27 and AGS cells inhibited proliferation and migratory potential. Intriguingly, epithelial-mesenchymal-transition (EMT) features were attenuated in the FTO-KD GC cells. On the other hand, FTO-overexpression in MKN28 cells enhanced their aggressive phenotype. Finally, to confirm our in-vitro findings, FTO suppression led to significant tumor growth inhibition in a HGC27 xenograft model.
Conclusion: We demonstrate that m6A regulators may serve as promising prognostic biomarkers in GC. Moreover, our functional studies reveal that FTO possesses oncogenic role and may be a promising therapeutic target associated with EMT-alterations in GC.
- Index Term 1: gastric cancer
- Index Term 2: FTO