The role of the globular heads of the C1q receptor in HPV-16 E2-induced human cervical squamous carcinoma cell apoptosis via a mitochondria-dependent pathway

Background: Human papillomavirus type-16 (HPV-16) E2 protein acts as a transcriptional modulator and plays a key role in regulating many biological responses. The purpose of this study was to investigate the relationship between HPV-16 E2, the receptor for the globular heads of human C1q (gC1qR) gene expression, mitochondrial dysfunction and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa). Methods: HPV-16 E2 and gC1qR expression was examined using real-time PCR and western blot analysis. Apoptosis in C33a and SiHa cells was assessed by flow cytometry. Mitochondrial function was detected via ROS generation, the amount of cytosolic Ca2+, and changes in the mitochondrial membrane potential (Delta psi m). Results: The expression of the HPV-16 E2 and gC1qR gene significantly decreased in human cervical squamous carcinoma samples relative to the non-cancerous cervix samples. C33a and SiHa cells that were transfected with a vector encoding HPV-16 E2 displayed significantly increased gC1qR gene expression and mitochondrial dysfunction as well as an up-regulation of cellular apoptosis, which was abrogated by the addition of gC1qR small-interfering RNA (siRNA). Conclusions: These data support a mechanism whereby gC1qR plays an important role in HPV-16 E2-induced human cervical squamous carcinoma cell apoptosis via a mitochondria-dependent pathway.