Abstract
BackgroundHuman 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).MethodsHPV-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 (Δψm).ResultsThe 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).ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0286-y) contains supplementary material, which is available to authorized users.
Highlights
Human papillomavirus type-16 (HPV-16) E2 protein acts as a transcriptional modulator and plays a key role in regulating many biological responses
The expression of the human papillomavirus (HPV)-16 E2 and Globular heads of C1q receptor (gC1qR) gene in human cervical tissue To investigate the relationship between the expression of HPV-16 E2, gC1qR and human cervical squamous cell carcinoma, HPV-16 E2 and gC1qR expression levels were analysed in 30 cases of human cervical squamous cell carcinoma and 30 cases of non-cancerous cervix tissues
The results showed that the expression levels of HPV-16 E2 protein were significantly decreased in human cervical squamous cell carcinoma tissues (T) compared with non-cancerous cervix tissues (N)
Summary
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). The receptor for the globular head of C1q, gC1qR, was initially identified as a protein within the mitochondrial matrix [11] that could mediate many biological responses, including growth perturbations, morphological abnormalities and the initiation of apoptosis [12]. This study aimed to comprehensively identify the effect of the gC1qR gene on HPV-16 E2-induced apoptosis of cells and to investigate whether the gC1qR-induced biological changes acted through a mitochondriadependent pathway in HPV-16 E2-transfected cervical squamous carcinoma cells
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