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Published on: March 11, 2014
HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer
Xubin Liu1, Hanyu Ma1, Lingyan Fei1
1Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 People's Republic of China.
Abstract:
Cervical cancer is the fourth most common malignant tumor in women worldwide. The persistent infection of high-risk Human Papillomavirus (hrHPV) is considered to be the primary cause of this disease. As an innate immune receptor, the nucleotide-binding oligomerization domain protein-1 (NOD1) recognizes the pathogen-associated molecular pattern (PAMP), subsequently initiating immune responses. NOD1 is also involved in the apoptotic signaling pathway and mutates in many cancer cells. In the study, we revealed that NOD1 expression decreased during the progression of cervical intraepithelial neoplasia to cervical cancer and that HPV16 E6/E7 oncoproteins induced down-regulation of NOD1. Moreover, the activation of NOD1 promoted the apoptosis of HPV16-positive cervical cancer cells. The data indicated that the dysregulation of NOD1-mediated inflammation and apoptosis may contribute to cervical intraepithelial neoplasia progression and cervical cancer.
Insights
Nucleotide-binding oligomerization domain protein-1 (NOD1) is downregulated in cervical cancer, driven by HPV16 oncoproteins. NOD1 activation promotes apoptosis in HPV-positive cancer cells, suggesting its role in disease progression.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Cervical cancer is a major global health concern, primarily caused by persistent high-risk Human Papillomavirus (hrHPV) infection.
- Nucleotide-binding oligomerization domain protein-1 (NOD1) is an innate immune receptor involved in pathogen recognition and apoptosis, with known mutations in cancer cells.
Purpose of the Study:
- To investigate the role of NOD1 in cervical cancer progression.
- To determine the effect of HPV16 oncoproteins on NOD1 expression.
- To evaluate the impact of NOD1 activation on HPV16-positive cervical cancer cell apoptosis.
Main Methods:
- Analysis of NOD1 expression levels during cervical intraepithelial neoplasia and cervical cancer progression.
- Investigation of HPV16 E6/E7 oncoprotein-induced NOD1 down-regulation.
- Assessment of NOD1 activation effects on apoptosis in HPV16-positive cervical cancer cells.
Main Results:
- NOD1 expression was found to decrease with the progression from cervical intraepithelial neoplasia to cervical cancer.
- HPV16 E6/E7 oncoproteins were identified as inducers of NOD1 down-regulation.
- Activation of NOD1 was shown to promote apoptosis in HPV16-positive cervical cancer cells.
Conclusions:
- Dysregulation of NOD1-mediated inflammation and apoptosis may contribute to the progression of cervical intraepithelial neoplasia and cervical cancer.
- NOD1 represents a potential therapeutic target for HPV-associated cervical malignancies.
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