hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway

PurposeAccumulating literature has suggested that hZIP1 and HIF-1α play vital roles in the tumor process of clear cell renal cell carcinoma (ccRCC). However, the functional roles of hZIP1 and HIF-1α in ccRCC remain largely unknown.MethodsHIF-1α protein level was evaluated by a western blot in ccRCC...

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Autores principales:	Bo Zhan, Xiao Dong, Yulin Yuan, Zheng Gong, Bohan Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	anaerobic glycolysis ccRCC HIF-1α hZIP1 NF-kB pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/de7877a6bad5435482e1399457248009
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spelling	oai:doaj.org-article:de7877a6bad5435482e13994572480092021-12-02T05:42:52ZhZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway2234-943X10.3389/fonc.2021.759818https://doaj.org/article/de7877a6bad5435482e13994572480092021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.759818/fullhttps://doaj.org/toc/2234-943XPurposeAccumulating literature has suggested that hZIP1 and HIF-1α play vital roles in the tumor process of clear cell renal cell carcinoma (ccRCC). However, the functional roles of hZIP1 and HIF-1α in ccRCC remain largely unknown.MethodsHIF-1α protein level was evaluated by a western blot in ccRCC tissues and cell lines. ccRCC cell lines were transfected with HIF-1α-siRNA to downregulate the expression level of HIF-1α. Then the proliferative, migratory and invasive abilities of ccRCC cells in vitro were detected by real-time cell analysis (RTCA) assay, wound healing assay and transwell assay, respectively. The role of HIF-1α in vivo was explored by tumor implantation in nude mice. Then the effect on glycolysis‐related proteins was performed by western blot after hZIP1 knockdown (overexpression) or HIF-1α knockdown. The effect on NF‐kB pathway was detected after hZIP1 overexpression.ResultsHIF-1α was markedly downregulated in ccRCC tissues compared with normal areas. But HIF-1α presented almost no expression in HK-2 and ACHN cells. Immunofluorescence indicated HIF-1α and PDK1 expression in both the cytoplasm and nucleus in ccRCC cells. Downregulation of HIF-1α suppressed ccRCC cell proliferation, migration, and invasion and resulted in smaller implanted tumors in nude mice. Furthermore, hZIP1 knockdown elevated HIF-1α protein levels and PDK1 protein levels in ccRCC cells. Interestingly, a sharp downregulated expression of HIF-1α was observed after hZIP1 overexpression in OSRC-2 and 786-O cells, which resulted from a downtrend of NF-kB1 moving into the cell nucleus.ConclusionOur work has vital implications that hZIP1 suppresses ccRCC progression by inhibiting NF-kB/HIF-1α pathway.Bo ZhanXiao DongYulin YuanZheng GongBohan LiFrontiers Media S.A.articleanaerobic glycolysisccRCCHIF-1αhZIP1NF-kB pathwayNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	anaerobic glycolysis ccRCC HIF-1α hZIP1 NF-kB pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	anaerobic glycolysis ccRCC HIF-1α hZIP1 NF-kB pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Bo Zhan Xiao Dong Yulin Yuan Zheng Gong Bohan Li hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway
description	PurposeAccumulating literature has suggested that hZIP1 and HIF-1α play vital roles in the tumor process of clear cell renal cell carcinoma (ccRCC). However, the functional roles of hZIP1 and HIF-1α in ccRCC remain largely unknown.MethodsHIF-1α protein level was evaluated by a western blot in ccRCC tissues and cell lines. ccRCC cell lines were transfected with HIF-1α-siRNA to downregulate the expression level of HIF-1α. Then the proliferative, migratory and invasive abilities of ccRCC cells in vitro were detected by real-time cell analysis (RTCA) assay, wound healing assay and transwell assay, respectively. The role of HIF-1α in vivo was explored by tumor implantation in nude mice. Then the effect on glycolysis‐related proteins was performed by western blot after hZIP1 knockdown (overexpression) or HIF-1α knockdown. The effect on NF‐kB pathway was detected after hZIP1 overexpression.ResultsHIF-1α was markedly downregulated in ccRCC tissues compared with normal areas. But HIF-1α presented almost no expression in HK-2 and ACHN cells. Immunofluorescence indicated HIF-1α and PDK1 expression in both the cytoplasm and nucleus in ccRCC cells. Downregulation of HIF-1α suppressed ccRCC cell proliferation, migration, and invasion and resulted in smaller implanted tumors in nude mice. Furthermore, hZIP1 knockdown elevated HIF-1α protein levels and PDK1 protein levels in ccRCC cells. Interestingly, a sharp downregulated expression of HIF-1α was observed after hZIP1 overexpression in OSRC-2 and 786-O cells, which resulted from a downtrend of NF-kB1 moving into the cell nucleus.ConclusionOur work has vital implications that hZIP1 suppresses ccRCC progression by inhibiting NF-kB/HIF-1α pathway.
format	article
author	Bo Zhan Xiao Dong Yulin Yuan Zheng Gong Bohan Li
author_facet	Bo Zhan Xiao Dong Yulin Yuan Zheng Gong Bohan Li
author_sort	Bo Zhan
title	hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway
title_short	hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway
title_full	hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway
title_fullStr	hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway
title_full_unstemmed	hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway
title_sort	hzip1 inhibits progression of clear cell renal cell carcinoma by suppressing nf-kb/hif-1α pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/de7877a6bad5435482e1399457248009
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hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway

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