Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21

p53/p21 signaling plays a vital role in pancreatic cancer (PC) progression. ZWINT was shown to function as an oncoprotein in the progression of multiple cancers. However, the involvement of ZWINT and p53 activation in the progression of PC remains poorly understood. Bioinformatics and tissue array c...

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Autores principales:	Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ZWINT pancreatic cancer HIF1α p53/p21 proliferation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/96f607549ad349099503b88f6c04e2b5
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spelling	oai:doaj.org-article:96f607549ad349099503b88f6c04e2b52021-11-30T18:47:04ZHypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p212296-634X10.3389/fcell.2021.682131https://doaj.org/article/96f607549ad349099503b88f6c04e2b52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.682131/fullhttps://doaj.org/toc/2296-634Xp53/p21 signaling plays a vital role in pancreatic cancer (PC) progression. ZWINT was shown to function as an oncoprotein in the progression of multiple cancers. However, the involvement of ZWINT and p53 activation in the progression of PC remains poorly understood. Bioinformatics and tissue array chip analyses were performed to evaluate ZWINT expression in pancreatic cancer. ZWINT mRNA and protein expression were evaluated in normoxia and hypoxia. CHIP was used to evaluate HIF1α interaction with the ZWINT promoter. CCK8, colony formation, EDU, and cell cycle analysis were used to examine PC cell proliferation. Immunoprecipitation and immunofluorescence were used to examine the interaction of ZWINT, MDM2, and p53. p53 activity was evaluated by q-PCR and luciferase assay. Protein degradation and ubiquitination assays were used to analyze the role of ZWINT in p53 ubiquitination. ZWINT was overexpressed in pancreatic cancer and induced in hypoxia. ZWINT promoted pancreatic cancer growth and cell cycle progression. Bioinformatic analysis revealed that ZWINT may regulate the p53 signal pathway. ZWINT interacts with p53 and promotes its ubiquitination and degradation. ZWINT promoted proliferation via p53/p21. Immunohistochemistry of clinical specimens revealed that that ZWINT expression was significantly negatively correlated with p53/p21. Our data showed that hypoxia regulates the expression of ZWINT, which activated p53/p21 signaling pathway to promote PC growth.Peng ChenPeng ChenZhiwei HeZhiwei HeJie WangJian XuXueyi JiangYankun ChenXinyuan LiuJianxin JiangFrontiers Media S.A.articleZWINTpancreatic cancerHIF1αp53/p21proliferationBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ZWINT pancreatic cancer HIF1α p53/p21 proliferation Biology (General) QH301-705.5
spellingShingle	ZWINT pancreatic cancer HIF1α p53/p21 proliferation Biology (General) QH301-705.5 Peng Chen Peng Chen Zhiwei He Zhiwei He Jie Wang Jian Xu Xueyi Jiang Yankun Chen Xinyuan Liu Jianxin Jiang Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
description	p53/p21 signaling plays a vital role in pancreatic cancer (PC) progression. ZWINT was shown to function as an oncoprotein in the progression of multiple cancers. However, the involvement of ZWINT and p53 activation in the progression of PC remains poorly understood. Bioinformatics and tissue array chip analyses were performed to evaluate ZWINT expression in pancreatic cancer. ZWINT mRNA and protein expression were evaluated in normoxia and hypoxia. CHIP was used to evaluate HIF1α interaction with the ZWINT promoter. CCK8, colony formation, EDU, and cell cycle analysis were used to examine PC cell proliferation. Immunoprecipitation and immunofluorescence were used to examine the interaction of ZWINT, MDM2, and p53. p53 activity was evaluated by q-PCR and luciferase assay. Protein degradation and ubiquitination assays were used to analyze the role of ZWINT in p53 ubiquitination. ZWINT was overexpressed in pancreatic cancer and induced in hypoxia. ZWINT promoted pancreatic cancer growth and cell cycle progression. Bioinformatic analysis revealed that ZWINT may regulate the p53 signal pathway. ZWINT interacts with p53 and promotes its ubiquitination and degradation. ZWINT promoted proliferation via p53/p21. Immunohistochemistry of clinical specimens revealed that that ZWINT expression was significantly negatively correlated with p53/p21. Our data showed that hypoxia regulates the expression of ZWINT, which activated p53/p21 signaling pathway to promote PC growth.
format	article
author	Peng Chen Peng Chen Zhiwei He Zhiwei He Jie Wang Jian Xu Xueyi Jiang Yankun Chen Xinyuan Liu Jianxin Jiang
author_facet	Peng Chen Peng Chen Zhiwei He Zhiwei He Jie Wang Jian Xu Xueyi Jiang Yankun Chen Xinyuan Liu Jianxin Jiang
author_sort	Peng Chen
title	Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
title_short	Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
title_full	Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
title_fullStr	Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
title_full_unstemmed	Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
title_sort	hypoxia-induced zwint mediates pancreatic cancer proliferation by interacting with p53/p21
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/96f607549ad349099503b88f6c04e2b5
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Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21

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