Department of Pathology, School of Medicine, Jinan University, Guangzhou, China.
J Cancer Res Clin Oncol. 2019 Jan;145(1):19-29. doi: 10.1007/s00432-018-2796-0. Epub 2018 Nov 21.
The fat mass- and obesity-associated (FTO) gene on chromosome 16q12.2 shows an intimate association with obesity and body mass index. Recently, research into the FTO gene and its expression product has attracted widespread interest due to the identification of FTO as an N6-methyladenosine (m6A) demethylase. FTO primarily regulates the m6A levels of downstream targets via their 3' untranslated regions. FTO not only plays a critical role in obesity-related diseases but also is involved in the occurrence, development and prognosis of many types of cancer, such as acute myeloid leukaemia, glioblastoma and breast cancer. Currently, studies indicate that FTO is a crucial component of m6A modification, it regulates cancer stem cell function, and promotes the growth, self-renewal and metastasis of cancer cells. In this review, we summarized and analysed the data regarding the structural features and biological functions of FTO as well as its association with different cancers and possible molecular mechanisms.
We systematically reviewed the related literatures regarding FTO and its demethylation activity in many pathologic and physiological processes, especially in cancer-related diseases based on PubMed databases in this article.
Mounting evidence indicated that FTO plays a critical role in occurrence, progression and treatment of various cancers, even acting as a cancer oncogene in acute myeloid leukaemia, research on which is no longer restricted to metabolic diseases such as obesity and diabetes.
Considering FTO's critical role in many diseases, FTO may become a new promising target for the diagnosis and treatment of various diseases in the near future, especially for specific types of cancers, such as acute myeloid leukaemia, glioblastoma and breast cancer.
染色体 16q12.2 上的肥胖相关基因（FTO）与肥胖和体重指数密切相关。最近，由于鉴定出 FTO 是 N6-甲基腺苷（m6A）去甲基酶，因此对 FTO 基因及其表达产物的研究引起了广泛关注。FTO 主要通过下游靶标 3'非翻译区调节 m6A 水平。FTO 不仅在肥胖相关疾病中起关键作用，而且还参与多种癌症的发生、发展和预后，如急性髓系白血病、胶质母细胞瘤和乳腺癌。目前的研究表明，FTO 是 m6A 修饰的关键组成部分，它调节癌症干细胞功能，并促进癌细胞的生长、自我更新和转移。在这篇综述中，我们总结和分析了有关 FTO 的结构特征和生物学功能及其与不同癌症的关联以及可能的分子机制的数据。
我们系统地回顾了基于 PubMed 数据库的关于 FTO 及其在许多病理和生理过程中的去甲基化活性的相关文献，特别是在癌症相关疾病方面。
越来越多的证据表明，FTO 在各种癌症的发生、进展和治疗中起着关键作用，甚至在急性髓系白血病中作为癌基因发挥作用，对其研究不再仅限于肥胖和糖尿病等代谢疾病。
鉴于 FTO 在许多疾病中的关键作用，FTO 可能在不久的将来成为诊断和治疗各种疾病的新的有前途的靶点，特别是对于特定类型的癌症，如急性髓系白血病、胶质母细胞瘤和乳腺癌。
