Abstract
BackgroundThe globular heads of the human C1q receptor (gC1qR) localize predominantly to the mitochondrial matrix. gC1qR mediates many biological responses, including growth perturbation, morphological abnormalities and the initiation of apoptosis. The purpose of this study was to investigate the relationship between mitochondrial dysfunction, p53 status and gC1qR expression and the regulation of apoptosis in human cervical squamous carcinoma cells (C33a and SiHa).MethodsHere, gC1qR expression was examined in human cervical tissues using real-time PCR and Western blot analysis. Apoptotic death of C33a and SiHa cells was assessed by flow cytometric analysis that detected the subG1 population. Mitochondrial function was assessed via ROS generation, the content of cytosolic Ca2+, and the change in mitochondrial membrane potential (Δψm). The viability and migration of C33a and SiHa cells were detected via the water-soluble tetrazolium salt (WST-1) assay and the transwell assay, respectively.ResultsgC1qR expression was decreased in cervical squamous cell carcinoma tissues compared with normal tissues. C33a and SiHa cells transfected with a vector encoding gC1qR displayed mitochondrial dysfunction and apoptosis, which was abrogated by the addition of a mutant form of p53 or p53 small interference RNA (siRNA). Furthermore, upon overexpression of gC1qR, cell viability and migration were significantly enhanced, and the apoptosis of C33a and SiHa cells were decreased when cells were treated with mutant p53 or p53 siRNA.ConclusionsThese data support a mechanism whereby gC1qR induces apoptosis through the mitochondrial and p53-dependent pathways in cervical squamous cell carcinoma.
Highlights
The globular heads of the human C1q receptor localize predominantly to the mitochondrial matrix. gC1qR mediates many biological responses, including growth perturbation, morphological abnormalities and the initiation of apoptosis
The expression of gC1qR in human cervical tissues In order to investigate the levels of gC1qR gene and protein expression in human cervical squamous cell carcinomas, 30 cases of human cervical squamous cell carcinomas and surrounding non-neoplastic tissues were analysed by real-time quantitative polymerase chain reaction and Western blot (Figure 1)
The results showed that the mRNA expression and protein levels of gC1qR were significantly decreased in human cervical squamous cell carcinoma tissues (T) compared with the surrounding non-neoplastic tissues (N)
Summary
The globular heads of the human C1q receptor (gC1qR) localize predominantly to the mitochondrial matrix. gC1qR mediates many biological responses, including growth perturbation, morphological abnormalities and the initiation of apoptosis. The lack of preventive strategies, early diagnostic methods, and effective therapies to treat recurrent cervical tumours creates a pressing need to understand its pathogenesis and to identify molecular markers and targets for diagnosis and therapy [2,3]. This involves the expression of both proand anti-apoptotic proteins that remain largely unknown. GC1qR-induced T-cell dysfunction involves the induction of suppressor of cytokine signaling (SOCS), a powerful inhibitor of cytokine signalling, which represents a novel mechanism of action [6] Examples of such responses include growth perturbation, morphological abnormalities and initiation of apoptosis [7]. The present study assessed the effect of gC1qR on the apoptosis of cervical squamous carcinoma cells, and investigated the gC1qR-induced activation of the p53-dependent pathway
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