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. 2021 Mar;236(3):2087-2098.
doi: 10.1002/jcp.29995. Epub 2020 Aug 4.

YEATS2 is a target of HIF1α and promotes pancreatic cancer cell proliferation and migration

Zhirui Zeng  1   2 , Shan Lei  2 , Zhiwei He  3 , Tengxiang Chen  2 , Jianxin Jiang  1   4
Affiliations

YEATS2 is a target of HIF1α and promotes pancreatic cancer cell proliferation and migration

Zhirui Zeng et al. J Cell Physiol. 2021 Mar.

Abstract

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.

Keywords: HIF1α; YEATS; cell migration; cell proliferation; hypoxia; pancreatic cancer.

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