Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, 730000, China.
Department of Pharmacy, The First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, Jiangxi, 341000, China.
Commun Biol. 2024 Jul 2;7(1):800. doi: 10.1038/s42003-024-06477-y.
Gastric cancer (GC) is the 5 most prevalent cancer and the 4 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.
胃癌（GC）是全球第 5 大常见癌症和第 4 大与癌症相关的主要死亡原因。肥胖相关蛋白（FTO）作为第一个被鉴定的 m6A 去甲基化酶，在癌症的发生和发展中起着重要作用。因此，我们研究了 FTO 在 GC 肿瘤发生和进展中的生物学功能和致癌机制。在我们的研究中，FTO 在 GC 组织和细胞中表达明显上调。FTO 的上调与 GC 患者的晚期神经侵犯、肿瘤大小、淋巴结转移和不良预后有关，并促进了 GC 细胞的活力、集落形成、迁移和侵袭。在机制上，FTO 靶向特异性蛋白 1 和 Aurora 激酶 B，导致共济失调毛细血管扩张突变和 P38 的磷酸化以及 P53 的去磷酸化。总之，m6A 去甲基酶 FTO 通过调节 SP1-AURKB-ATM 通路促进 GC 的肿瘤发生和进展，这可能突出了 FTO 作为 GC 患者治疗反应和预后的诊断生物标志物的潜力。
