Liu Xubin, Ma Hanyu, Fei Lingyan, Jiang Mengjie, Xia Meng, Bai Lihong, Pi Xufang, Chen Shangwu, Yu Li
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 People's Republic of China.
Infect Agent Cancer. 2020 Jan 30;15:6. doi: 10.1186/s13027-020-0272-3. eCollection 2020.
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.
宫颈癌是全球女性中第四大常见恶性肿瘤。高危型人乳头瘤病毒（hrHPV）的持续感染被认为是该疾病的主要病因。作为一种天然免疫受体，核苷酸结合寡聚化结构域蛋白1（NOD1）识别病原体相关分子模式（PAMP），随后启动免疫反应。NOD1也参与凋亡信号通路且在许多癌细胞中发生突变。在本研究中，我们发现NOD1表达在宫颈上皮内瘤变进展为宫颈癌的过程中降低，且HPV16 E6/E7癌蛋白诱导NOD1下调。此外，NOD1的激活促进了HPV16阳性宫颈癌细胞的凋亡。数据表明，NOD1介导的炎症和凋亡失调可能促成宫颈上皮内瘤变进展和宫颈癌。
