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DOI | 10.1038/ncomms14812 |
m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade | |
Yang, Seungwon1; Wei, Jiangbo2; Cui, Yan-Hong1; Parka, Gayoung3; Shah, Palak1,4; Deng, Yu5; Aplin, Andrew E.6,7; Lu, Zhike2; Hwang, Seungmin3; He, Chuan2,8; He, Yu-Ying1 | |
2019-06-25 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
英文摘要 | Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N-6-methyladenosine (m(6)A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-kappa B pathway. Knockdown of FTO increases m(6)A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m(6)A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFN gamma) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m(6)A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000472710900001 |
WOS关键词 | IMMUNE CHECKPOINT ; CD47 BLOCKADE ; IFN-GAMMA ; N-6-METHYLADENOSINE ; METHYLATION ; GENE ; ROLES ; RISK ; AXIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203249 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Chicago, Dept Med, Sect Dermatol, 5841 S Maryland Ave, Chicago, IL 60637 USA; 2.Univ Chicago, Dept Chem, Dept Biochem & Mol Biol, Inst Biophys Dynam, 5735 S Ellis Ave, Chicago, IL 60637 USA; 3.Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA; 4.Univ Chicago, Comm Mol Pathogenesis & Mol Med, Chicago, IL 60637 USA; 5.China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110122, Liaoning, Peoples R China; 6.Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA; 7.Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA; 8.Univ Chicago, Howard Hughes Med Inst, 5841 S Maryland Ave, Chicago, IL 60637 USA |
推荐引用方式 GB/T 7714 | Yang, Seungwon,Wei, Jiangbo,Cui, Yan-Hong,et al. m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Yang, Seungwon.,Wei, Jiangbo.,Cui, Yan-Hong.,Parka, Gayoung.,Shah, Palak.,...&He, Yu-Ying.(2019).m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade.NATURE COMMUNICATIONS,10. |
MLA | Yang, Seungwon,et al."m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade".NATURE COMMUNICATIONS 10(2019). |
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