Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors

Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis o...

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Autores principales:	Yaozhong Hu, Ema Romão, Cécile Vincke, Lea Brys, Yvon Elkrim, Marylène Vandevenne, Changxiao Liu, Serge Muyldermans
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	HIF-1α nanobodies transcriptional activation target genes Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/6f0151a9c47f46fca5f4ada2110b62ff
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spelling	oai:doaj.org-article:6f0151a9c47f46fca5f4ada2110b62ff2021-11-25T17:55:32ZIntrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors10.3390/ijms2222123351422-00671661-6596https://doaj.org/article/6f0151a9c47f46fca5f4ada2110b62ff2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12335https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis of tumor cells. Targeting and inhibiting the transcriptional activity of HIF-1 may provide an interesting strategy for cancer therapy. In the present study, an immune library and a synthetic library were constructed for the phage display selection of Nbs against recombinant PAS B domain protein (rPasB) of HIF-1α. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1α subunit. The inhibitory effect of the selected Nbs on HIF-1 induced activation of target genes has been evaluated after intracellular expression of these Nbs in HeLa cells. The dramatic inhibition of both intrabody formats on the expression of HIF-1-related target genes has been confirmed, which indicated the inhibitory efficacy of selected Nbs on the transcriptional activity of HIF-1.Yaozhong HuEma RomãoCécile VinckeLea BrysYvon ElkrimMarylène VandevenneChangxiao LiuSerge MuyldermansMDPI AGarticleHIF-1αnanobodiestranscriptional activationtarget genesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12335, p 12335 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIF-1α nanobodies transcriptional activation target genes Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	HIF-1α nanobodies transcriptional activation target genes Biology (General) QH301-705.5 Chemistry QD1-999 Yaozhong Hu Ema Romão Cécile Vincke Lea Brys Yvon Elkrim Marylène Vandevenne Changxiao Liu Serge Muyldermans Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors
description	Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis of tumor cells. Targeting and inhibiting the transcriptional activity of HIF-1 may provide an interesting strategy for cancer therapy. In the present study, an immune library and a synthetic library were constructed for the phage display selection of Nbs against recombinant PAS B domain protein (rPasB) of HIF-1α. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1α subunit. The inhibitory effect of the selected Nbs on HIF-1 induced activation of target genes has been evaluated after intracellular expression of these Nbs in HeLa cells. The dramatic inhibition of both intrabody formats on the expression of HIF-1-related target genes has been confirmed, which indicated the inhibitory efficacy of selected Nbs on the transcriptional activity of HIF-1.
format	article
author	Yaozhong Hu Ema Romão Cécile Vincke Lea Brys Yvon Elkrim Marylène Vandevenne Changxiao Liu Serge Muyldermans
author_facet	Yaozhong Hu Ema Romão Cécile Vincke Lea Brys Yvon Elkrim Marylène Vandevenne Changxiao Liu Serge Muyldermans
author_sort	Yaozhong Hu
title	Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors
title_short	Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors
title_full	Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors
title_fullStr	Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors
title_full_unstemmed	Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors
title_sort	intrabody targeting hif-1α mediates transcriptional downregulation of target genes related to solid tumors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6f0151a9c47f46fca5f4ada2110b62ff
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Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors

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