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

	YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression
	Shi, YL; Fan, SQ; Wu, MG; Zuo, ZX; Li, XY; Jiang, LP; Shen, QS; Xu, PF; Zeng, L; Zhou, YC; Huang, YC; Yang, ZZ; Zhou, JM; Gao, J; Zhou, H; Xu, SH; Ji, HB; Shi, P; Wu, DD; Yang, CP; Chen, YB
	2019
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	10 页码:-
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.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12989
专题	科研部门_肿瘤信号转导（陈勇彬）
推荐引用方式 GB/T 7714	Shi, YL,Fan, SQ,Wu, MG,et al. YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression[J]. NATURE COMMUNICATIONS,2019,10:-.
APA	Shi, YL.,Fan, SQ.,Wu, MG.,Zuo, ZX.,Li, XY.,...&Chen, YB.(2019).YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression.NATURE COMMUNICATIONS,10,-.
MLA	Shi, YL,et al."YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression".NATURE COMMUNICATIONS 10(2019):-.

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