Abstract
BackgroundHuman 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).MethodsgC1qR 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.ResultsC33a 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.ConclusionThese 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.
Highlights
Human papillomavirus type 16 (HPV 16) E2 protein is a multifunctional DNA-binding protein
Antibodies directed against globular heads of C1q receptor (gC1qR), phosphorylated p38 p38 mitogen-activated protein kinase (MAPK) (p*-p38 MAPK), phosphorylated jun N-terminal kinase (JNK) (p*-JNK), total p38 MAPK, total JNK and actin were purchased from Santa Cruz (Santa Cruz, CA, USA) and Cell Signaling Technology. pcDNA-human papillomavirus (HPV) 16 E2 and pcDNA-HPV 16 E2 mutant plasmids were kindly supplied by Hangzhou Hibio Bio-tech Co., Ltd. gC1qR small interfering RNA and negative siRNA were synthesised by Wuhan Genesil Biotechnology Co., Ltd (Wuhan, China)
The data are presented in Figure 1A; HPV 16 E2 expression decreased cell viability compared with the unmodified media group, while there was no change in cell viability in the empty vector or HPV 16 E2 mutant group compared with the unmodified media group
Summary
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). Most HPV infections are eliminated through anti-viral immune responses, and only a percentage of HPVinfected women with oncogenic types have persistent infections that cause high-grade squamous intraepithelial lesions [10,11]. GC1qR mediates many biological responses, including inflammation, infection and immune regulation [15]. Examples of such responses include phagocytosis and apoptotic cell uptake [16]
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