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.

CONCLUSION:

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: Ling-juan Gao, Ping-qing Gu, Wei Zhao, Wen-yan Ding, Xue-qing Zhao, Shu-yu Guo, Tian-ying Zhong
• Journal: Journal of translational medicine (J Transl Med) Vol. 11 Pg. 118 (May 08 2013) ISSN: 1479-5876 [Electronic] England
• PMID: 23651874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• E2 protein, Human papillomavirus type 16
• Membrane Glycoproteins
• Oncogene Proteins, Viral
• Receptors, Complement
• complement 1q receptor
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4

Topics

• Apoptosis
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Cell Survival
• DNA-Binding Proteins (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Human papillomavirus 16
• Humans
• MAP Kinase Kinase 4 (metabolism)
• Membrane Glycoproteins (metabolism)
• Oncogene Proteins, Viral (metabolism)
• Protein Structure, Tertiary
• Receptors, Complement (metabolism)
• Signal Transduction
• Uterine Cervical Neoplasms (metabolism, pathology)
• p38 Mitogen-Activated Protein Kinases (metabolism)