Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor

Based on our initial bioinformatics finding of the upregulated expression of sentrin-specific protease 1 (SENP1) and cyclin E1 (CCNE1) in Wilms tumor, this study aimed to illustrate the molecular mechanism of SENP1 in Wilms tumor, which involved the hypoxia-inducible factor 1α (HIF-1α)/stanniocalcin...

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Autores principales:	Shibo Zhu, Jinhua Hu, Yanhong Cui, Shen Liang, Xiaofeng Gao, Jin Zhang, Wei Jia
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Wilms tumor SENP1 HIF-1α SUMOylation STC1 CCNE1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f67ea92b186f4418bb3411eb1cdb3116
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spelling	oai:doaj.org-article:f67ea92b186f4418bb3411eb1cdb31162021-11-06T04:32:01ZKnockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor2372-770510.1016/j.omto.2021.07.007https://doaj.org/article/f67ea92b186f4418bb3411eb1cdb31162021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001042https://doaj.org/toc/2372-7705Based on our initial bioinformatics finding of the upregulated expression of sentrin-specific protease 1 (SENP1) and cyclin E1 (CCNE1) in Wilms tumor, this study aimed to illustrate the molecular mechanism of SENP1 in Wilms tumor, which involved the hypoxia-inducible factor 1α (HIF-1α)/stanniocalcin-1 (STC1)/CCNE1 axis. Wilms tumor and adjacent normal tissues were clinically collected. Gain- and loss-of-function assays were performed to evaluate the effects of the regulatory axis on malignant phenotypes of Wilms tumor cells. A mouse model of Wilms tumor xenografts was further established for in vivo substantiation. Overexpression of CCNE1 and SENP1 occurred in Wilms tumor tissues and cells. Silencing SENP1 inhibited viability and enhanced cell-cycle arrest of Wilms tumor cells. SENP1 promoted STC1 expression and upregulated CCNE1 by driving the small ubiquitin-like modifier (SUMO)ylation of HIF-1α, which ultimately promoted the malignant phenotypes of Wilms tumor cells. It was further confirmed that silencing SENP1 downregulated the expression of CCNE1 and restricted tumorigenicity of Wilms tumor cells in vivo. Taken together, SENP1 elevated STC1 expression by driving the SUMOylation of HIF-1α, thereby upregulating the expression of CCNE1 and ultimately promoting the development of Wilms tumor.Shibo ZhuJinhua HuYanhong CuiShen LiangXiaofeng GaoJin ZhangWei JiaElsevierarticleWilms tumorSENP1HIF-1αSUMOylationSTC1CCNE1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 355-366 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Wilms tumor SENP1 HIF-1α SUMOylation STC1 CCNE1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Wilms tumor SENP1 HIF-1α SUMOylation STC1 CCNE1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Shibo Zhu Jinhua Hu Yanhong Cui Shen Liang Xiaofeng Gao Jin Zhang Wei Jia Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor
description	Based on our initial bioinformatics finding of the upregulated expression of sentrin-specific protease 1 (SENP1) and cyclin E1 (CCNE1) in Wilms tumor, this study aimed to illustrate the molecular mechanism of SENP1 in Wilms tumor, which involved the hypoxia-inducible factor 1α (HIF-1α)/stanniocalcin-1 (STC1)/CCNE1 axis. Wilms tumor and adjacent normal tissues were clinically collected. Gain- and loss-of-function assays were performed to evaluate the effects of the regulatory axis on malignant phenotypes of Wilms tumor cells. A mouse model of Wilms tumor xenografts was further established for in vivo substantiation. Overexpression of CCNE1 and SENP1 occurred in Wilms tumor tissues and cells. Silencing SENP1 inhibited viability and enhanced cell-cycle arrest of Wilms tumor cells. SENP1 promoted STC1 expression and upregulated CCNE1 by driving the small ubiquitin-like modifier (SUMO)ylation of HIF-1α, which ultimately promoted the malignant phenotypes of Wilms tumor cells. It was further confirmed that silencing SENP1 downregulated the expression of CCNE1 and restricted tumorigenicity of Wilms tumor cells in vivo. Taken together, SENP1 elevated STC1 expression by driving the SUMOylation of HIF-1α, thereby upregulating the expression of CCNE1 and ultimately promoting the development of Wilms tumor.
format	article
author	Shibo Zhu Jinhua Hu Yanhong Cui Shen Liang Xiaofeng Gao Jin Zhang Wei Jia
author_facet	Shibo Zhu Jinhua Hu Yanhong Cui Shen Liang Xiaofeng Gao Jin Zhang Wei Jia
author_sort	Shibo Zhu
title	Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor
title_short	Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor
title_full	Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor
title_fullStr	Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor
title_full_unstemmed	Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor
title_sort	knockdown of senp1 inhibits hif-1α sumoylation and suppresses oncogenic ccne1 in wilms tumor
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f67ea92b186f4418bb3411eb1cdb3116
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Knockdown of SENP1 inhibits HIF-1α SUMOylation and suppresses oncogenic CCNE1 in Wilms tumor

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