m6A去甲基化酶FTO在肿瘤中的作用及研究进展

Role of m6A Demethylase FTO in Tumors and It’s Research Progress

关键词:  肥胖相关蛋白  m⁶A修饰  肿瘤  化疗耐药

Key words:  fat mass and obesity-associated protein(FTO)  m⁶A modification  tumor  chemotherapy resistance

摘要:

肥胖相关蛋白（fat mass and obesity-associated protein，FTO）是一种位于染色体16q12.2上的N6-甲基腺苷（m⁶A）去甲基酶，以往的研究证实FTO可通过3’非翻译区域调节下游的m⁶A水平来影响肥胖。随着研究的不断深入，研究者们发现，m⁶A甲基化这一表观遗传修饰能通过调控肿瘤基因、抑肿瘤基因的mRNA分子的表达水平调控肿瘤的发生发展。FTO作为m⁶A修饰的重要组成部分，参与调控多种肿瘤的发生、发展及其预后。目前研究表明，FTO能够通过不同方式（影响肿瘤细胞生长和增殖、抑制细胞分化、干预肿瘤干细胞自我更新、影响肿瘤转移和放化疗敏感性等）参与调控多种肿瘤发生发展。因此，FTO有望在不久的将来成为诊断和治疗肿瘤的新靶点，特别是针对某些特定类型的肿瘤，如急性髓系白血病、胶质母细胞癌和乳腺癌等，这对于肿瘤的诊疗具有重要的理论意义和应用价值。本文拟通过对目前有关FTO的研究进行整理和分析，对FTO在肿瘤中的作用及其研究进展进行了综述。

Abstract:

Fat mass and obesity-associated protein(FTO) on chromosome 16q12.2 is an N6-methyladenosine(m⁶A) demethylase, some studies confirmed FTO regulated the m⁶A levels of downstream targets via their 3'untranslated regions to influence obesity. With the development of research, researchers have found that epigenetic modification of m⁶A methylation can regulate the occurrence and development of tumors by regulating the tumor suppressor genes and mRNA expression level of oncogenes. FTO is a crucial component of m⁶A modification, it regulates the occurrence, development and prognosis of various tumors. Current evidence indicate that FTO plays a critical role in occurrence, progression and treatment of various tumors via different ways, such as via affecting the growth and proliferation of tumor cells, inhibiting cell differentiation, intervening in the self-renewal of tumor stem cells, affecting tumor metastasis and radio-chemotherapy sensitivity. FTO may become a new promising target for the diagnosis and treatment of various tumors in the near future, especially for specific types of tumor, such as acute myeloid leukaemia, glioblastoma and breast cancer, etc. This has important theoretical significance and application value for the diagnosis and treatment of tumors. In this paper, the role of FTO in tumor and its research progress are reviewed through sorting out and analyzing the current researches on it.