HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress

Abstract Background The key role of hypoxia‐inducible factor 2alpha (HIF2α) in the process of renal cancer has been confirmed. In the field of tumour research, oxidative stress is also considered to be an important influencing factor. However, the relationship and biological benefits of oxidative st...

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Autores principales:	Jian Shi, Zhiyong Xiong, Keshan Wang, Changfei Yuan, Yu Huang, Wen Xiao, Xiangui Meng, Zhixian Chen, Qingyang Lv, Daojia Miao, Huageng Liang, Tianbo Xu, Kairu Xie, Hongmei Yang, Xiaoping Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	hypoxia‐inducible factor 2alpha (HIF2α) NUDT1 oxidative stress reactive oxygen species sirtuin 3 (SIRT3) Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8d973470d7fa4310a693013981f9acd3
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spelling	oai:doaj.org-article:8d973470d7fa4310a693013981f9acd32021-11-30T07:25:38ZHIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress2001-132610.1002/ctm2.592https://doaj.org/article/8d973470d7fa4310a693013981f9acd32021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.592https://doaj.org/toc/2001-1326Abstract Background The key role of hypoxia‐inducible factor 2alpha (HIF2α) in the process of renal cancer has been confirmed. In the field of tumour research, oxidative stress is also considered to be an important influencing factor. However, the relationship and biological benefits of oxidative stress and HIF2α in ccRCC remain unclear. This research attempts to explore the effect of oxidative stress on the cancer‐promoting effect of HIF2α in ccRCC and reveal its mechanism of action. Methods The bioinformatics analysis for ccRCC is based on whole transcriptome sequencing and TCGA database. The detection of the expression level of related molecules is realised by western blot and PCR. The expression of Nucleoside diphosphate‐linked moiety X‐type motif 1 (NUDT1) was knocked down by lentiviral infection technology. The functional role of NUDT1 were further investigated by CCK8 assays, transwell assays and cell oxidative stress indicator detection. The exploration of related molecular mechanisms is realised by Luciferase assays and Chromatin immunoprecipitation (ChIP) assays. Results Molecular screening based on knockdown HIF2α sequencing data and oxidative stress related data sets showed that NUDT1 is considered to be an important molecule for the interaction of HIF2α with oxidative stress. Subsequent experimental results showed that NUDT1 can cooperate with HIF2α to promote the progression of ccRCC. And this biological effect was found to be caused by the oxidative stress regulated by NUDT1. Mechanistically, HIF2α transcription activates the expression of NUDT1, thereby inhibiting oxidative stress and promoting the progression of ccRCC. Conclusions This research clarified a novel mechanism by which HIF2α stabilises sirtuin 3 (SIRT3) through direct transcriptional activation of NUDT1, thereby inhibiting oxidative stress to promote the development of ccRCC. It provided the possibility for the selection of new therapeutic targets for ccRCC and the study of combination medication regimens.Jian ShiZhiyong XiongKeshan WangChangfei YuanYu HuangWen XiaoXiangui MengZhixian ChenQingyang LvDaojia MiaoHuageng LiangTianbo XuKairu XieHongmei YangXiaoping ZhangWileyarticlehypoxia‐inducible factor 2alpha (HIF2α)NUDT1oxidative stressreactive oxygen speciessirtuin 3 (SIRT3)Medicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoxia‐inducible factor 2alpha (HIF2α) NUDT1 oxidative stress reactive oxygen species sirtuin 3 (SIRT3) Medicine (General) R5-920
spellingShingle	hypoxia‐inducible factor 2alpha (HIF2α) NUDT1 oxidative stress reactive oxygen species sirtuin 3 (SIRT3) Medicine (General) R5-920 Jian Shi Zhiyong Xiong Keshan Wang Changfei Yuan Yu Huang Wen Xiao Xiangui Meng Zhixian Chen Qingyang Lv Daojia Miao Huageng Liang Tianbo Xu Kairu Xie Hongmei Yang Xiaoping Zhang HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress
description	Abstract Background The key role of hypoxia‐inducible factor 2alpha (HIF2α) in the process of renal cancer has been confirmed. In the field of tumour research, oxidative stress is also considered to be an important influencing factor. However, the relationship and biological benefits of oxidative stress and HIF2α in ccRCC remain unclear. This research attempts to explore the effect of oxidative stress on the cancer‐promoting effect of HIF2α in ccRCC and reveal its mechanism of action. Methods The bioinformatics analysis for ccRCC is based on whole transcriptome sequencing and TCGA database. The detection of the expression level of related molecules is realised by western blot and PCR. The expression of Nucleoside diphosphate‐linked moiety X‐type motif 1 (NUDT1) was knocked down by lentiviral infection technology. The functional role of NUDT1 were further investigated by CCK8 assays, transwell assays and cell oxidative stress indicator detection. The exploration of related molecular mechanisms is realised by Luciferase assays and Chromatin immunoprecipitation (ChIP) assays. Results Molecular screening based on knockdown HIF2α sequencing data and oxidative stress related data sets showed that NUDT1 is considered to be an important molecule for the interaction of HIF2α with oxidative stress. Subsequent experimental results showed that NUDT1 can cooperate with HIF2α to promote the progression of ccRCC. And this biological effect was found to be caused by the oxidative stress regulated by NUDT1. Mechanistically, HIF2α transcription activates the expression of NUDT1, thereby inhibiting oxidative stress and promoting the progression of ccRCC. Conclusions This research clarified a novel mechanism by which HIF2α stabilises sirtuin 3 (SIRT3) through direct transcriptional activation of NUDT1, thereby inhibiting oxidative stress to promote the development of ccRCC. It provided the possibility for the selection of new therapeutic targets for ccRCC and the study of combination medication regimens.
format	article
author	Jian Shi Zhiyong Xiong Keshan Wang Changfei Yuan Yu Huang Wen Xiao Xiangui Meng Zhixian Chen Qingyang Lv Daojia Miao Huageng Liang Tianbo Xu Kairu Xie Hongmei Yang Xiaoping Zhang
author_facet	Jian Shi Zhiyong Xiong Keshan Wang Changfei Yuan Yu Huang Wen Xiao Xiangui Meng Zhixian Chen Qingyang Lv Daojia Miao Huageng Liang Tianbo Xu Kairu Xie Hongmei Yang Xiaoping Zhang
author_sort	Jian Shi
title	HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress
title_short	HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress
title_full	HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress
title_fullStr	HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress
title_full_unstemmed	HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress
title_sort	hif2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of nudt1 to reduce oxidative stress
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/8d973470d7fa4310a693013981f9acd3
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HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress

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