• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

FTO作为一种N-甲基腺苷RNA去甲基化酶在急性髓系白血病中发挥致癌作用。

FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N-Methyladenosine RNA Demethylase.

作者信息

Li Zejuan, Weng Hengyou, Su Rui, Weng Xiaocheng, Zuo Zhixiang, Li Chenying, Huang Huilin, Nachtergaele Sigrid, Dong Lei, Hu Chao, Qin Xi, Tang Lichun, Wang Yungui, Hong Gia-Ming, Huang Hao, Wang Xiao, Chen Ping, Gurbuxani Sandeep, Arnovitz Stephen, Li Yuanyuan, Li Shenglai, Strong Jennifer, Neilly Mary Beth, Larson Richard A, Jiang Xi, Zhang Pumin, Jin Jie, He Chuan, Chen Jianjun

机构信息

Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.

Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA.

出版信息

Cancer Cell. 2017 Jan 9;31(1):127-141. doi: 10.1016/j.ccell.2016.11.017. Epub 2016 Dec 22.

DOI:10.1016/j.ccell.2016.11.017
PMID:28017614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5234852/
Abstract

N-Methyladenosine (mA) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of mA in cancer have been limited. Here we show that FTO, as an mA demethylase, plays a critical oncogenic role in acute myeloid leukemia (AML). FTO is highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations. FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and RARA by reducing mA levels in these mRNA transcripts. Collectively, our study demonstrates the functional importance of the mA methylation and the corresponding proteins in cancer, and provides profound insights into leukemogenesis and drug response.

摘要

N-甲基腺苷（mA）是哺乳动物mRNA中最普遍的内部修饰。尽管其在各种基本生物过程中具有重要功能，但关于癌症中mA的研究仍然有限。在此我们表明，FTO作为一种mA去甲基化酶，在急性髓系白血病（AML）中发挥关键的致癌作用。FTO在伴有t(11q23)/MLL重排、t(15;17)/PML-RARA、FLT3-ITD和/或NPM1突变的AML中高表达。FTO通过降低这些mRNA转录本中的mA水平来调节ASB2和RARA等靶标的表达，从而增强白血病致癌基因介导的细胞转化和白血病发生，并抑制全反式维甲酸（ATRA）诱导的AML细胞分化。总的来说，我们研究证明了mA甲基化及相应蛋白在癌症中的功能重要性，并为白血病发生和药物反应提供了深刻见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/0480151d1a6a/nihms837597f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/8ad928c35cad/nihms837597f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/84fb13c61b09/nihms837597f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/3a9b249b8ea8/nihms837597f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/ae5d824330c9/nihms837597f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/fc38dc374a43/nihms837597f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/d04d837997a0/nihms837597f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/c07c26f16dbc/nihms837597f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/0480151d1a6a/nihms837597f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/8ad928c35cad/nihms837597f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/84fb13c61b09/nihms837597f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/3a9b249b8ea8/nihms837597f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/ae5d824330c9/nihms837597f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/fc38dc374a43/nihms837597f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/d04d837997a0/nihms837597f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/c07c26f16dbc/nihms837597f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/5234852/0480151d1a6a/nihms837597f8.jpg

相似文献

1
FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N-Methyladenosine RNA Demethylase.FTO作为一种N-甲基腺苷RNA去甲基化酶在急性髓系白血病中发挥致癌作用。
Cancer Cell. 2017 Jan 9;31(1):127-141. doi: 10.1016/j.ccell.2016.11.017. Epub 2016 Dec 22.
2
Saikosaponin D exhibits anti-leukemic activity by targeting FTO/mA signaling.柴胡皂苷 D 通过靶向 FTO/mA 信号通路发挥抗白血病活性。
Theranostics. 2021 Mar 31;11(12):5831-5846. doi: 10.7150/thno.55574. eCollection 2021.
3
Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia.小分子靶向致癌性 FTO 去甲基酶在急性髓系白血病中的作用。
Cancer Cell. 2019 Apr 15;35(4):677-691.e10. doi: 10.1016/j.ccell.2019.03.006.
4
[Research Progress of m6A Demethylase FTO and Its Inhibitors in Acute Myeloid Leukemia --Review].[6-甲基腺嘌呤去甲基化酶FTO及其抑制剂在急性髓系白血病中的研究进展——综述]
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):902-906. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.042.
5
FTO-Dependent N-Methyladenosine Regulates Cardiac Function During Remodeling and Repair.FTO 依赖性 N6-甲基腺苷调节重塑和修复过程中心脏功能。
Circulation. 2019 Jan 22;139(4):518-532. doi: 10.1161/CIRCULATIONAHA.118.033794.
6
METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA mA Modification.METTL14 通过 mRNA mA 修饰抑制造血干/祖细胞分化并促进白血病发生。
Cell Stem Cell. 2018 Feb 1;22(2):191-205.e9. doi: 10.1016/j.stem.2017.11.016. Epub 2017 Dec 28.
7
mA demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.mA 去甲基酶 FTO 通过调节 MZF1 表达促进肺鳞癌肿瘤进展。
Biochem Biophys Res Commun. 2018 Aug 25;502(4):456-464. doi: 10.1016/j.bbrc.2018.05.175. Epub 2018 Jun 2.
8
FTO-Dependent -Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling.FTO 依赖性 -m6A 修饰通过阻断 cAMP 信号抑制卵巢癌细胞干细胞自我更新。
Cancer Res. 2020 Aug 15;80(16):3200-3214. doi: 10.1158/0008-5472.CAN-19-4044. Epub 2020 Jun 30.
9
Novel positioning from obesity to cancer: FTO, an mA RNA demethylase, regulates tumour progression.肥胖与癌症的新关联：FTO，一种 mA RNA 去甲基酶，调节肿瘤进展。
J Cancer Res Clin Oncol. 2019 Jan;145(1):19-29. doi: 10.1007/s00432-018-2796-0. Epub 2018 Nov 21.
10
FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner.FTO 通过依赖于 N6-甲基腺苷的方式降低 APOE mRNA 的稳定性，从而抑制甲状腺乳头状癌细胞的糖酵解和生长。
J Exp Clin Cancer Res. 2022 Jan 28;41(1):42. doi: 10.1186/s13046-022-02254-z.

引用本文的文献

1
Crosstalk between noncoding RNAs and autophagy in renal cell carcinoma: Deciphering molecular pathways and therapeutic prospects.肾细胞癌中非编码RNA与自噬之间的相互作用：解读分子途径及治疗前景
Cancer Cell Int. 2025 Sep 2;25(1):318. doi: 10.1186/s12935-025-03957-x.
2
Evidence human FTO catalyses hydroxylation of N6-methyladenosine without direct formation of a demethylated product contrasting with ALKBH5/2/3 and bacterial AlkB.有证据表明，与ALKBH5/2/3和细菌AlkB不同，人类FTO催化N6-甲基腺苷的羟基化反应，但不会直接形成去甲基化产物。
Nucleic Acids Res. 2025 Aug 27;53(16). doi: 10.1093/nar/gkaf813.
3
FTO inhibited miR-487a-3p biosynthesis via N6-methyladenosine-dependent pathway to promote WNT5A-mediated osteogenic differentiation of adipose-derived stem cells.

本文引用的文献

1
miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia.miR-22 在急性髓系白血病中具有强大的抗肿瘤作用和治疗潜力。
Nat Commun. 2016 Apr 26;7:11452. doi: 10.1038/ncomms11452.
2
Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m⁶A-demethylation of NANOG mRNA.缺氧通过HIF依赖和ALKBH5介导的NANOG mRNA的m⁶A去甲基化诱导乳腺癌干细胞表型。
Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):E2047-56. doi: 10.1073/pnas.1602883113. Epub 2016 Mar 21.
3
5' UTR m(6)A Promotes Cap-Independent Translation.
FTO通过N6-甲基腺苷依赖途径抑制miR-487a-3p的生物合成，以促进WNT5A介导的脂肪来源干细胞的成骨分化。
Hum Cell. 2025 Aug 27;38(5):152. doi: 10.1007/s13577-025-01273-0.
4
N-methyladenosine attenuates tumor-associated macrophages M2 polarization via suppressing the translation of Snail.N-甲基腺苷通过抑制Snail的翻译来减弱肿瘤相关巨噬细胞的M2极化。
Sci China Life Sci. 2025 Aug 21. doi: 10.1007/s11427-024-2897-y.
5
Emerging implications of N6-methyladenosine in prostate cancer progression and treatment.N6-甲基腺嘌呤在前列腺癌进展和治疗中的新意义。
Cell Death Discov. 2025 Aug 19;11(1):391. doi: 10.1038/s41420-025-02680-w.
6
The FTO-YTHDF2 axis drives immune evasion and tumor progression in hepatocellular carcinoma via m6A-dependent FLAD1 regulation.FTO-YTHDF2轴通过m6A依赖的FLAD1调控驱动肝细胞癌的免疫逃逸和肿瘤进展。
J Mol Histol. 2025 Aug 19;56(5):267. doi: 10.1007/s10735-025-10557-6.
7
Small-molecule and peptide inhibitors of m6A regulators.m6A调控因子的小分子和肽类抑制剂
Front Oncol. 2025 Aug 1;15:1629864. doi: 10.3389/fonc.2025.1629864. eCollection 2025.
8
FTO degrader impairs ribosome biogenesis and protein translation in acute myeloid leukemia.FTO降解剂损害急性髓系白血病中的核糖体生物合成和蛋白质翻译。
Sci Adv. 2025 Aug 15;11(33):eadv7648. doi: 10.1126/sciadv.adv7648.
9
N6-methyladenosine-modified circDCP2 promotes carbon black nanoparticle-induced malignancy in human bronchial epithelial cells via PI3K-AKT pathway and macrophage homeostasis.N6-甲基腺苷修饰的环状DCP2通过PI3K-AKT信号通路和巨噬细胞稳态促进炭黑纳米颗粒诱导的人支气管上皮细胞恶性转化。
J Nanobiotechnology. 2025 Aug 7;23(1):555. doi: 10.1186/s12951-025-03632-3.
10
ALKBH1 drives tumorigenesis and drug resistance via tRNA decoding reprogramming and codon-biased translation.ALKBH1通过tRNA解码重编程和密码子偏向性翻译驱动肿瘤发生和耐药性。
Cancer Discov. 2025 Aug 4. doi: 10.1158/2159-8290.CD-24-1043.
5'非翻译区N6-甲基腺苷促进不依赖帽子结构的翻译。
Cell. 2015 Nov 5;163(4):999-1010. doi: 10.1016/j.cell.2015.10.012. Epub 2015 Oct 22.
4
Dynamic m(6)A mRNA methylation directs translational control of heat shock response.动态的N⁶-甲基腺苷（m⁶A）信使核糖核酸（mRNA）甲基化指导热休克反应的翻译控制。
Nature. 2015 Oct 22;526(7574):591-4. doi: 10.1038/nature15377. Epub 2015 Oct 12.
5
Acute Myeloid Leukemia.急性髓系白血病
N Engl J Med. 2015 Sep 17;373(12):1136-52. doi: 10.1056/NEJMra1406184.
6
RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation.RNA N6-甲基腺苷甲基化在转录后基因表达调控中的作用
Genes Dev. 2015 Jul 1;29(13):1343-55. doi: 10.1101/gad.262766.115.
7
N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency.N⁶-甲基腺苷调节信使核糖核酸的翻译效率。
Cell. 2015 Jun 4;161(6):1388-99. doi: 10.1016/j.cell.2015.05.014.
8
Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells.维甲酸和三氧化二砷促使突变型 NPM1 降解，导致 AML 细胞凋亡。
Blood. 2015 May 28;125(22):3447-54. doi: 10.1182/blood-2014-11-612416. Epub 2015 Mar 23.
9
N6-methyladenosine marks primary microRNAs for processing.N6-甲基腺苷标记初级微小RNA以便进行加工。
Nature. 2015 Mar 26;519(7544):482-5. doi: 10.1038/nature14281. Epub 2015 Mar 18.
10
Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells.三氧化二砷和全反式维甲酸靶向 NPM1 突变癌蛋白水平，并诱导 NPM1 突变 AML 细胞凋亡。
Blood. 2015 May 28;125(22):3455-65. doi: 10.1182/blood-2014-11-611459. Epub 2015 Mar 20.