title: Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus.
abstract: 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.
authors: Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai, China.|Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
authors: Lu
authors: L
authors: Dai
authors: Department of Pediatrics, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Jing
authors: J
authors: Qiao
authors: William Carey University College of Osteopathic Medicine, Hattiesburg, MS, USA.
authors: David
authors: D
authors: Nguyen
authors: Department of Pathology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
authors: Amanda P
authors: AP
authors: Struckhoff
authors: Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
authors: Lisa
authors: L
authors: Doyle
authors: Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
authors: Karlie
authors: K
authors: Bonstaff
authors: Department of Pathology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
authors: Luis
authors: L
authors: Del Valle
authors: Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
authors: Chris
authors: C
authors: Parsons
authors: Department of Regenerative Medicine & Cell Biology, Medical University of South Carolina and Hollings Cancer Center, Charleston, SC, USA.
authors: Bryan P
authors: BP
authors: Toole
authors: Department of Molecular Genetics Microbiology, University of Florida, Gainesville, FL, USA.
authors: Rolf
authors: R
authors: Renne
authors: Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai, China.|Departments of Microbiology/Immunology/Parasitology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
authors: Zhiqiang
authors: Z
authors: Qin
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D017209:Apoptosis; D051926:Basigin / Q000378:metabolism*; D063646:Carcinogenesis / Q000187:drug effects; D049109:Cell Proliferation; D004249:DNA Damage / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology* / Q000821:virology; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis / Q000139:chemically induced; D009687:Nuclear Proteins / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000473:pathology* / Q000821:virology
chemical_list: D000956:Antigens, Viral; C497887:Bsg protein, mouse; D008665:Metalloporphyrins; D009687:Nuclear Proteins; D011524:Protoporphyrins; D034741:RNA, Small Interfering; C109540:latency-associated nuclear antigen; D051926:Basigin; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1
keywords: HO-1; KSHV; Kaposi’s sarcoma; SnPP