脂肪量和肥胖相关基因在肿瘤中的研究进展

Research advances of fat mass and obesity-associated gene in tumors

2007年脂肪量和肥胖相关(fat mass and obesity-associated,FTO)基因首次在欧洲人群中被鉴定为脂肪风险基因,而后又被发现是第一个信使RNA N6-甲基腺苷(N6-methyladenosine,m6A)去甲基化酶,可使m6A去甲基化。FTO基因具有强连锁不平衡阻滞,目前已经鉴定出参与肥胖发展的FTO单核苷酸多态性(single nucleotide polymorphisms,SNPs),某些FTO SNPs亦显示出与癌症易感性相关。已有研究显示,FTO表达水平变化或功能失调时,可作为抑癌或致癌基因参与多种肿瘤的发生、发展,与肿瘤细胞的增殖、分化以及对缺氧应激的耐受性等密切相关。随着研究的深入,FTO或能为肿瘤的诊断和治疗提供新靶点。本文就FTO基因在肿瘤中的研究进展予以综述,旨在为肿瘤的分子病理诊断和分子靶向治疗寻找新方向。

In 2007,the fat mass and obesity-associated (FTO) gene was first identified as a fat risk gene in the European population,and was later found to be the first mRNA N6-methyladenosine (m6A) demethylase,which could demethylate m6A.The FTO gene has strong linkage disequilibrium block,in which single nucleotide polymorphisms (SNPs) of FTOs involved in obesity development have been identified,and some FTO SNPs have also been shown to be associated with cancer susceptibility.Studies have demonstrated that FTO expression levels or dysfunction could be used as tumor suppressor or oncogene involving in the occurrence and development of a variety of tumors,and is closely related to tumor cell proliferation and differentiation,tolerance to hypoxia stress,etc.With the deepening of researches,FTO could provide a new target for tumor diagnosis and treatment.This article reviewed the research progress of FTO in tumors,aiming to find a new direction for molecular pathological diagnosis and molecular targeted therapy of tumors.