Liu Jie, Li Li, Luo Ning, Liu Qi, Liu Li, Chen Dandan, Cheng Zhongping, Xi Xiaowei
Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, P.R. China.
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Clinical College of Nanjing Medical University, Shanghai 200072, P.R. China.
Exp Ther Med. 2021 Feb;21(2):163. doi: 10.3892/etm.2020.9594. Epub 2020 Dec 21.
Cancer antigen 125 (CA125), encoded by the mucin 16 cell surface associated (MUC16) gene, has been widely used as a biomarker for ovarian cancer (OC) screening. However, it has yet to be elucidated as to why its levels increase with tumor progression as well as with certain other non-malignant conditions. Based on our knowledge of the inflammatory microenvironment (IME) in OC, HEY cells were treated with several inflammation-associated factors as well as their antagonists, and it was observed that inflammation-associated factors upregulated MUC16 gene expression. Considering the role of nuclear factor (NF)-κB in the inflammatory signaling network and our previous research on OC, chromatin immunoprecipitation was performed, and it was observed that activated NF-κB bound to the MUC16 gene promoter and enhanced its expression, thereby elevating secreted CA125 levels. These findings demonstrated that IME and MUC16 gene expression were associated in OC, partly elucidating the role of IME in tumor progression, explaining the elevated serum CA125 levels in some non-malignant conditions, and confirming IME as a potential target for OC therapy.
癌抗原125（CA125）由黏蛋白16细胞表面相关（MUC16）基因编码，已被广泛用作卵巢癌（OC）筛查的生物标志物。然而，关于其水平为何会随着肿瘤进展以及某些其他非恶性疾病而升高，仍有待阐明。基于我们对OC炎症微环境（IME）的了解，用几种炎症相关因子及其拮抗剂处理HEY细胞，观察到炎症相关因子上调了MUC16基因的表达。考虑到核因子（NF）-κB在炎症信号网络中的作用以及我们之前对OC的研究，进行了染色质免疫沉淀，观察到活化的NF-κB与MUC16基因启动子结合并增强其表达，从而提高分泌的CA125水平。这些发现表明，IME与OC中的MUC16基因表达相关，部分阐明了IME在肿瘤进展中的作用，解释了某些非恶性疾病中血清CA125水平升高的原因，并证实IME是OC治疗的潜在靶点。
