Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been repor...

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Main Authors:	Dai, Lu, Qiao, Jing, Nguyen, David, Struckhoff, Amanda P., Doyle, Lisa, Bonstaff, Karlie, Del Valle, Luis, Parsons, Chris, Toole, Bryan P., Renne, Rolf, Qin, Zhiqiang
Format:	Online
Language:	English
Published:	Impact Journals LLC 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891132/

id	pubmed-4891132
recordtype	oai_dc
spelling	pubmed-48911322016-06-23 Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus Dai, Lu Qiao, Jing Nguyen, David Struckhoff, Amanda P. Doyle, Lisa Bonstaff, Karlie Del Valle, Luis Parsons, Chris Toole, Bryan P. Renne, Rolf Qin, Zhiqiang Research Paper Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions. We previously demonstrate that the multifunctional glycoprotein CD147 is required for KSHV/LANA-induced endothelial cell invasiveness. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly elevated in both CD147-overexpressing and KSHV-infected HUVEC cells when compared to control cells. In the current study, we further identify the regulation of HO-1 expression and mediated cellular functions by both CD147 and KSHV-encoded LANA proteins. Targeting HO-1 by either RNAi or the chemical inhibitor, SnPP, effectively induces cell death of KSHV-infected endothelial cells (the major cellular components of KS) through DNA damage and necrosis process. By using a KS-like nude mouse model, we found that SnPP treatment significantly suppressed KSHV-induced tumorigenesis in vivo. Taken together, our data demonstrate the important role of HO-1 in the pathogenesis and tumorigenesis of KSHV-infected endothelial cells, the underlying regulatory mechanisms for HO-1 expression and targeting HO-1 may represent a promising therapeutic strategy against KSHV-related malignancies. Impact Journals LLC 2016-02-07 /pmc/articles/PMC4891132/ /pubmed/26859574 http://dx.doi.org/10.18632/oncotarget.7227 Text en Copyright: © 2016 Dai et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Dai, Lu Qiao, Jing Nguyen, David Struckhoff, Amanda P. Doyle, Lisa Bonstaff, Karlie Del Valle, Luis Parsons, Chris Toole, Bryan P. Renne, Rolf Qin, Zhiqiang
spellingShingle	Dai, Lu Qiao, Jing Nguyen, David Struckhoff, Amanda P. Doyle, Lisa Bonstaff, Karlie Del Valle, Luis Parsons, Chris Toole, Bryan P. Renne, Rolf Qin, Zhiqiang Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus
author_facet	Dai, Lu Qiao, Jing Nguyen, David Struckhoff, Amanda P. Doyle, Lisa Bonstaff, Karlie Del Valle, Luis Parsons, Chris Toole, Bryan P. Renne, Rolf Qin, Zhiqiang
author_sort	Dai, Lu
title	Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus
title_short	Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus
title_full	Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus
title_fullStr	Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus
title_full_unstemmed	Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus
title_sort	role of heme oxygenase-1 in the pathogenesis and tumorigenicity of kaposi's sarcoma-associated herpesvirus
description	Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions. We previously demonstrate that the multifunctional glycoprotein CD147 is required for KSHV/LANA-induced endothelial cell invasiveness. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly elevated in both CD147-overexpressing and KSHV-infected HUVEC cells when compared to control cells. In the current study, we further identify the regulation of HO-1 expression and mediated cellular functions by both CD147 and KSHV-encoded LANA proteins. Targeting HO-1 by either RNAi or the chemical inhibitor, SnPP, effectively induces cell death of KSHV-infected endothelial cells (the major cellular components of KS) through DNA damage and necrosis process. By using a KS-like nude mouse model, we found that SnPP treatment significantly suppressed KSHV-induced tumorigenesis in vivo. Taken together, our data demonstrate the important role of HO-1 in the pathogenesis and tumorigenesis of KSHV-infected endothelial cells, the underlying regulatory mechanisms for HO-1 expression and targeting HO-1 may represent a promising therapeutic strategy against KSHV-related malignancies.
publisher	Impact Journals LLC
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891132/
_version_	1613588106857938944

Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus

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