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YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression

文献类型：期刊论文

作者Shi, Yulin6,7; Fan, Songqing8; Wu, Mengge9; Zuo, Zhixiang10; Li, Xingyang10; Jiang, Liping6; Shen, Qiushuo6,7; Xu, Peifang6; Zeng, Lin6,7; Zhou, Yongchun9
刊名NATURE COMMUNICATIONS
出版日期2019-10-25
卷号10页码:14
ISSN号2041-1723
DOI10.1038/s41467-019-12801-6
通讯作者Wu, Dong-Dong(wudongdong@mail.kiz.ac.cn) ; Yang, Cuiping(cuipingyang@mail.kiz.ac.cn) ; Chen, Yongbin(ynchen@mail.kiz.ac.cn)
英文摘要Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan domestic mammals compared to reciprocal lowlanders. Furthermore, m(6)A modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.
WOS关键词MESSENGER-RNA ; RESISTANCE ; ANGIOGENESIS ; TRANSLATION ; PLASTICITY ; SELECTION ; IMPACT ; NRF2 ; ROS
资助项目National Key Research and Development Program of China, Stem Cell and Translational Research[2016YFA0100900] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB13000000] ; National Nature Science Foundation of China[U1502224] ; National Nature Science Foundation of China[81772996] ; National Nature Science Foundation of China[81672764] ; National Nature Science Foundation of China[U1702283] ; National Nature Science Foundation of China[81773218] ; Yunnan Applied Basic Research Projects[2016FA009] ; Yunnan Province High-level Talents Introduced Program[2013HA021] ; Chinese Academy of Sciences Western Light Program, Youth Innovation Promotion Association, CAS ; National Natural Science Foundation of China[91731303] ; National Natural Science Foundation of China[31525014] ; UK Royal Society-Newton Advanced Fellowship[NAF/R1/191094]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000492835100030
源URL[http://119.78.100.183/handle/2S10ELR8/281878]  
专题中国科学院上海药物研究所
通讯作者Wu, Dong-Dong; Yang, Cuiping; Chen, Yongbin
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Key Lab Computat Biol, Shanghai 200031, Peoples R China
3.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China
4.Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
5.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China
6.Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China
7.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650204, Yunnan, Peoples R China
8.Cent S Univ, Second Xiangya Hosp, Dept Pathol, Changsha 410000, Hunan, Peoples R China
9.Kunming Med Univ, Kunming 650223, Yunnan, Peoples R China
10.Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China
推荐引用方式
GB/T 7714		 Shi, Yulin,Fan, Songqing,Wu, Mengge,et al. YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression[J]. NATURE COMMUNICATIONS,2019,10:14.
APA Shi, Yulin.,Fan, Songqing.,Wu, Mengge.,Zuo, Zhixiang.,Li, Xingyang.,...&Chen, Yongbin.(2019).YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression.NATURE COMMUNICATIONS,10,14.
MLA Shi, Yulin,et al."YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression".NATURE COMMUNICATIONS 10(2019):14.

入库方式： OAI收割

来源：上海药物研究所

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