脂肪质量和肥胖相关蛋白在肥胖相关肿瘤中的研究进展
【摘要】 脂肪质量和肥胖相关蛋白(FTO)是首个被确认的肥胖易感基因,其RNA去甲基化酶功能在肿瘤中作用复杂。FTO通过调控mRNA的m6A修饰水平,影响致癌基因稳定性和信号通路,驱动肿瘤细胞代谢重编程、增殖、侵袭及化疗耐药。在肥胖相关肿瘤中,FTO表达呈组织特异性:在子宫内膜癌、结直肠癌、胰腺癌和乳腺癌中高表达,通过激活免疫抑制微环境和糖酵解促进肿瘤进展;在甲状腺癌中低表达,通过调控铁死亡抑制恶变;在卵巢癌和肝癌中则发挥促癌或抑癌的双重作用,取决于分子背景和亚型。FTO水平与肿瘤分期、转移及预后密切相关,可作为新型预后标志物。靶向FTO的小分子抑制剂已在临床前模型中显现抗肿瘤潜力,为肥胖相关肿瘤的精准干预提供新策略。文章综述FTO在肥胖相关肿瘤中的分子机制与转化前景,为精准医疗策略提供理论支持。【关键词】 脂肪质量和肥胖相关蛋白;m6A去甲基化酶;肥胖相关肿瘤;治疗靶点;卵巢癌;甲状腺癌;乳腺癌
Research progress on fat mass and obesity-associated protein in obesity-related tumors
LI Zelong1,2,3, HUANG Junwei2,3, CHEN Hao2,3, YING Yong1,3, XIE Yang1,3, ZENG Xiangtai1,2,3
(1.Department of Thyroid Hernia Surgery, First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, China;
2.Key Laboratory of Thyroid Tumor of Ganzhou, Ganzhou 341000, China; 3.Institute of Thyroid Diseases, Gannan Medical College,
Ganzhou 341000, China)
Corresponding author: ZENG Xiangtai, E-mail: xiangtai.zeng@gmu.edu.cn
【Abstract】 Fat mass and obesity-associated protein (FTO), the first identified obesity-susceptibility gene, exerts complex roles in tumors via its RNA demethylase function. Through modulation of N6-methyladenosine (m6A) modification levels on mRNA ......
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