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YEATS2 is a target of HIF1α and promotes pancreatic cancer cell proliferation and migration.
Journal of Cellular Physiology ( IF 5.6 ) Pub Date : 2020-08-04 , DOI: 10.1002/jcp.29995
Zhirui Zeng 1, 2 , Shan Lei 2 , Zhiwei He 3 , Tengxiang Chen 2 , Jianxin Jiang 1, 4
Affiliation  

Hypoxia is involved in the development of pancreatic cancer (PC). The responses of hypoxia‐associated genes and their regulated mechanisms are largely unknown. In this study, through bioinformatic analysis and quantitative real‐time polymerase chain reaction, the YEATS domain containing 2 (YEATS2) was determined to be a key hypoxia‐associated gene. It was increased in PC cells under hypoxia, upregulated in PC tissues, and predicted poor outcome. YEATS2 inhibition decreased the proliferation and migration of PC cells under both normoxia and hypoxia in vitro as well as proliferation and metastasis in vivo. We found that hypoxia‐inducible factor 1α (HIF1α) regulated the expression of YEATS2 via binding to the hypoxia response element (HRE) of YEATS2 and coexpressed with YEATS2 in PC tissues. Overexpression of YEATS2 blocked the inhibitory effects of HIF1α silence on PC cell proliferation and migration under hypoxia. Collectively, our study revealed that YEATS2 is a target gene of HIF1α and promotes PC development under hypoxia.

中文翻译:

YEATS2 是 HIF1α 的靶标并促进胰腺癌细胞增殖和迁移。

缺氧参与胰腺癌 (PC) 的发展。缺氧相关基因的反应及其调节机制在很大程度上是未知的。本研究通过生物信息学分析和定量实时聚合酶链反应,确定含有2的YEATS结构域(YEATS2)是一个关键的缺氧相关基因。它在缺氧条件下在 PC 细胞中增加,在 PC 组织中上调,并预测不良结果。YEATS2抑制降低了体外常氧和缺氧条件下PC细胞的增殖和迁移以及体内增殖和转移。我们发现,低氧诱导因子1α(HIF1α)上调的表达YEATS2通过结合的低氧反应元件(HRE)YEATS2并在 PC 组织中与YEATS2共表达。YEATS2的过表达阻断了HIF1α沉默对缺氧条件下PC细胞增殖和迁移的抑制作用。总的来说,我们的研究表明YEATS2HIF1α的靶基因,在缺氧条件下促进 PC 发育。
更新日期:2020-08-04
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