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

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.

Characterization of the microRNA profile in early-stage cervical squamous cell carcinoma by next-generation sequencing

“…Early in 2006, Engelbrecht et al indicated the involvement of MAPK in cervical cancer and demonstrated the correlation between the activity of MAPK and apoptosis in the disease process (49). The HPV 16 E2 protein may induce apoptosis by inhibiting MAPK signaling in CSCC (50). However, playing a role in cervical cancer carcinogenesis, the expression level of MAPK may serve as a marker for cervical cancer progression (51,52) and its inhibitors have shown the potential to be useful for cervical cancer therapy (53).…”

Downregulation of NOB1 inhibits proliferation and promotes apoptosis in human oral squamous cell carcinoma

“…In view of the importance of MAPK in cell proliferation and differentiation, many viruses hijack the MAPK pathway in the progress of virus induced tumor genesis. MAPK was reported to participate in human papillomavirus type (HPV)-induced human cervical squamous carcinoma (29,30). It is hypothesized that HPV infection is one of the histopathologic risk factors in young OSCC patients (1,31).…”

Designing of CD8⁺ and CD8⁺-overlapped CD4⁺ epitope vaccine by targeting late and early proteins of human papillomavirus

“…62,63 systems biology-based virtual cancer pathway prediction and kinetics A literature survey was performed to collect the required information about the selected protein sequences to design and predict the peptides involved in biochemical pathways. [64][65][66][67][68][69][70][71][72][73][74] A mathematical and computational model of the entire HPV45 infection signaling pathway interacting with specific genes in the presence of peptides was developed and was visualized using CellDesigner v4.4 modeling tool. 75 Nodes in the pathway represented the entities, and edges represented connectivity of one node to another, which was closely related to each other.…”