title: Cell growth inhibition in HPV 18 positive uveal melanoma cells by E6/E7 siRNA.
abstract: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. However, the molecular development of UM is not fully understood and current therapeutic modalities result in poor outcomes. Increasingly, data have shown that human papillomaviruses (HPVs) contribute to the development of cervical cancer and other malignancies, and the key viral oncoprotein E6/E7 has become the target of gene therapy in HPV-related cancers. In this study, we identified HPV 18 infection in the UM cell line, VUP, for the first time and silenced HPV 18 E6/E7 expression using siRNA. Our results demonstrated that down regulation of HPV 18E6/E7 led to growth inhibition and cell cycle block in VUP cells by activation of the p53 and Rb pathways. We propose that HPV is possibly involved in the development of UM, and provide a novel target for the development of therapeutic strategies for UM.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Cun
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D006131:Growth Inhibitors / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000502:physiology*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000098943:Uveal Melanoma
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D006131:Growth Inhibitors; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53