title: The role of globular heads of the C1q receptor in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis is associated with p38 MAPK/JNK activation.
abstract: BACKGROUND
  Human papillomavirus type 16 (HPV 16) E2 protein is a multifunctional DNA-binding protein. HPV 16 E2 regulates many biological responses, including DNA replication, gene expression, and apoptosis. The purpose of this study was to investigate the relationship among the receptor for globular heads of the human C1q (gC1qR) gene expression, HPV 16 E2 transfection and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa).
  
  
  METHODS
  gC1qR expression was examined in C33a and SiHa cells using real-time PCR and Western blot analysis. Apoptosis of C33a and SiHa cells was assessed by flow cytometry. C33a and SiHa cell viability, migration and proliferation were detected using the water-soluble tetrazolium salt (WST-1) assay, a transwell assay and 3H-thymidine incorporation into DNA (3H-TdR), respectively.
  
  
  RESULTS
  C33a and SiHa cells that were transfected with a vector encoding HPV 16 E2 displayed significantly increased gC1qR gene expression and p38 mitogen-activated protein kinase (p38 MAPK)/c-jun N-terminal kinase (JNK) activation as well as up-regulation of cellular apoptosis, which was abrogated by the addition of gC1qR small interfering RNA (siRNA). Furthermore, the changes in C33a and SiHa cell viability, migration and proliferation that were observed upon HPV 16 E2 transfection were abrogated by SB203580 (a p38 MAPK inhibitor) or SP600125 (a JNK inhibitor) treatment.
  
  
  CONCLUSIONS
  These data support a mechanism whereby HPV 16 E2 induces apoptosis by silencing the gC1qR gene or inhibiting p38 MAPK/JNK signalling in cervical squamous cell carcinoma.
authors: State Key Laboratory of Reproductive Medicine, Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Tianfei Alley, Nanjing Mochou Road, Nanjing, 210004, PR China. gaolingjuan@njmu.edu.cn
authors: Ling-juan
authors: LJ
authors: Gao
authors: Ping-qing
authors: PQ
authors: Gu
authors: Wei
authors: W
authors: Zhao
authors: Wen-yan
authors: WY
authors: Ding
authors: Xue-qing
authors: XQ
authors: Zhao
authors: Shu-yu
authors: SY
authors: Guo
authors: Tian-ying
authors: TY
authors: Zhong
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052162:Human papillomavirus 16; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011951:Receptors, Complement / Q000378:metabolism*; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D011951:Receptors, Complement; C032402:complement 1q receptor; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
references: Obstet Gynecol. 2013 Feb;121(2 Pt 1):321-329
references: 23344282
references: Ginekol Pol. 2012 Aug;83(8):572-5
references: 23342878
references: Cancer Res. 2004 Feb 15;64(4):1299-306
references: 14973072
references: Virus Res. 2002 Nov;89(2):213-28
references: 12445661
references: J Biol Chem. 1997 Sep 26;272(39):24363-70
references: 9305894
references: Drug Healthc Patient Saf. 2012;4:167-72
references: 23152707
references: Virology. 2012 Jan 5;422(1):114-24
references: 22056390
references: J Virol. 1989 Oct;63(10):4417-21
references: 2476573
references: Cancer Res. 2012 Oct 1;72(19):4993-5003
references: 22991302
references: Virology. 2012 Feb 5;423(1):38-48
references: 22177699
references: EMBO J. 2012 May 22;31(14):3212-27
references: 22617423
references: J Biol Chem. 2012 Jun 15;287(25):21303-15
references: 22539350
references: Cancer Res. 2006 Jun 1;66(11):5555-9
references: 16740689
references: Nucleic Acids Res. 2012 Oct;40(19):9717-37
references: 22904065
references: J Transl Med. 2012 Dec 26;10:255
references: 23268996
references: Immunobiology. 2007;212(4-5):333-42
references: 17544818
references: Microbiol Mol Biol Rev. 2004 Jun;68(2):362-72
references: 15187189
references: Cancer Sci. 2012 Dec;103(12):2127-34
references: 22937809
references: Saudi Med J. 2012 Dec;33(12):1270-7
references: 23232673
references: Int J Gynaecol Obstet. 2012 Jun;117(3):289-90
references: 22425011
references: Adv Exp Med Biol. 2013;735:97-110
references: 23402021
references: J Cell Sci. 2001 Jun;114(Pt 11):2115-23
references: 11493647
references: J Med Virol. 2013 Mar;85(3):472-82
references: 23280876
references: Int J Oncol. 2011 Nov;39(5):1265-72
references: 21725590
references: Cancer Lett. 2005 Nov 18;229(2):261-70
references: 16125299
references: Cancer Manag Res. 2012;4:269-79
references: 22977311
references: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1530-5
references: 19164550
references: Mol Cell Biol. 2010 Mar;30(6):1303-18
references: 20100866
references: J Virol. 2010 May;84(10):5131-9
references: 20237089
references: Curr Opin Obstet Gynecol. 2009 Feb;21(1):54-9
references: 19125004
references: J Androl. 2012 Jan-Feb;33(1):114-21
references: 21311052
references: J Biol Chem. 2012 Jun 1;287(23):19750-64
references: 22451658
references: Int Immunopharmacol. 2003 Jan;3(1):39-51
references: 12538033
references: Eur J Gynaecol Oncol. 2012;33(5):467-71
references: 23185789
references: Cell Physiol Biochem. 2012;30(5):1181-90
references: 23052251
references: Am J Transl Res. 2012;4(4):452-7
references: 23145213
references: Thromb Haemost. 2003 Feb;89(2):331-9
references: 12574814
references: Asian Pac J Cancer Prev. 2012;13(2):599-606
references: 22524831