title: The role of gC1qR in regulating survival of human papillomavirus 16 oncogene-transfected cervical cancer cells.
abstract: Human papillomavirus 16 (HPV-16) is strongly associated with the development of 50% of cervical cancers. The E6 and E7 proteins encoded by high-risk HPV types are associated with the immune evasion of cervical cancer cells, but the mechanism is poorly understood. The purpose of this study was to investigate whether cells transfected with E6 and E7 expression constructs reduce the expression of the globular heads of the C1q receptor (gC1qR), a mitochondrial surface protein overexpressed in certain cancer cells. First, C-33A cells were transiently transfected with the HPV-16 E6 and E7 oncogenes which resulted in gC1qR inhibition and a reduction in apoptosis. Second, gC1qR overexpression in cells showed that caspase-3 activation and mitochondrial dysfunction were involved in gC1qR-induced apoptosis. Cells transfected with a GFP-gC1qR vector resulted in upregulated gC1qR protein and a gradual increase in the generation of reactive oxygen species (ROS). Additionally, ROS generation and increased Ca2+ influx in mitochondria resulted in the loss of the mitochondrial transmembrane potential. Interestingly, when gC1qR was overexpressed in C-33A cells, apoptosis was significantly inhibited when cells were treated with metformin, which may protect mitochondrial function. These data suggest that gC1qR could play an important role in HPV-16-induced cervical cancer immune evasion depending on its level of expression and subcellular localisation.
authors: Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital, Nanjing, P.R. China.
authors: Ling-Juan
authors: LJ
authors: Gao
authors: Ping-Qing
authors: PQ
authors: Gu
authors: Wei-Min
authors: WM
authors: Fan
authors: Zhu
authors: Z
authors: Liu
authors: Feng
authors: F
authors: Qiu
authors: Yu-Zhu
authors: YZ
authors: Peng
authors: Xi-Rong
authors: XR
authors: Guo
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D042963:Electron Transport Complex II / Q000172:deficiency; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology* / Q000821:virology*
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D009856:Oncogene Proteins, Viral; D017382:Reactive Oxygen Species; C478189:respiratory complex II; D042963:Electron Transport Complex II; D002118:Calcium