YEATS2 is a target of HIF1α and promotes pancreatic cancer cell proliferation and migration
YEATS2 is a target of HIF1α and promotes pancreatic cancer cell proliferation and migration
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YEATS2 是 HIF1α 的靶标，促进胰腺癌细胞增殖和迁移
DOI：
10.1002/jcp.29995
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发表时间：
2020-08-04
影响因子：
5.6
通讯作者：
Jiang, Jianxin
中科院分区：
文献类型：
--
作者：
Zeng, Zhirui;Lei, Shan;Jiang, Jianxin
缺氧参与胰腺癌(PC)的发展。低氧相关基因的反应及其调控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实时定量聚合酶链反应，确定了YEATS结构域2 （YEATS2）是一个关键的缺氧相关基因。它在缺氧的PC细胞中升高，在PC组织中上调，预示着不良的预后。YEATS2抑制抑制了体外常氧和缺氧条件下PC细胞的增殖和迁移，以及体内的增殖和转移。我们发现缺氧诱导因子1 α (HIF1 α)通过结合YEATS2的缺氧反应元件（HRE）调控YEATS2的表达，并在PC组织中与YEATS2共表达。过表达YEATS2可阻断HIF1 α沉默对缺氧条件下PC细胞增殖和迁移的抑制作用。综上所述，我们的研究表明YEATS2是HIF1 α的靶基因，可促进缺氧条件下PC的发育。
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 1 alpha (HIF1 alpha) 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 HIF1 alpha silence on PC cell proliferation and migration under hypoxia. Collectively, our study revealed that YEATS2 is a target gene of HIF1 alpha and promotes PC development under hypoxia.