外泌体 NOX1 通过刺激宫颈癌中 ROS 的产生促进肿瘤相关巨噬细胞 M2 极化介导的癌症进展：一项初步研究。
Exosomal NOX1 promotes tumor-associated macrophage M2 polarization-mediated cancer progression by stimulating ROS production in cervical cancer: a preliminary study.
机构信息
Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
Eur J Med Res. 2023 Sep 7;28(1):323. doi: 10.1186/s40001-023-01246-9.
BACKGROUND
Cervical cancer the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020 for high rates of recurrence and metastasis. Identification of novel targets could aid in the prediction and treatment of cervical cancer. NADPH oxidase 1 (NOX1) gene-mediated production of reactive oxygen species (ROS) could induce migration and invasion of cervical cancer cells. Tumor-associated macrophages (TAMs) play important roles in cervical cancer. Tumor cell-derived exosomes mediate signal transduction between the tumor and tumor microenvironment. Elucidation of the mechanisms of NOX1-carrying exosomes involved in the regulation of TAMs may provide valuable insights into the progression of cervical cancer.
METHODS
Uniformly standardized mRNA data of pan-carcinoma from the UCSC database were downloaded. Expression of NOX1 in tumor and adjacent normal tissues for each tumor type was calculated using R language software and significant differences were analyzed. SNP data set were downloaded for all TCGA samples processed using MuTect2 software from GDC. Cell experiment and animal tumor formation experiment were used to evaluate whether exosomal NOX1 stimulating ROS production to promote M2 polarization of TAM in cervical cancer.
RESULTS
NOX1 is highly expressed with a low mutational frequency in pan-carcinoma. Upregulation of NOX1 may be associated with infiltration of M2-type macrophages in cervical cancer tissues, and NOX1 promotes malignant features of cervical cancer cells by stimulating ROS production. Exosomal NOX1 promotes M2 polarization of by stimulating ROS production. Exosomal NOX1 enhances progression of cervical cancer and M2 polarization in vivo by stimulating ROS production.
CONCLUSION
Exosomal NOX1 promotes TAM M2 polarization-mediated cancer progression through stimulating ROS production in cervical cancer.
背景
宫颈癌是全球女性中第四常见的癌症，也是第四大癌症死因，2020 年全球估计有 604,000 例新发病例和 342,000 例死亡病例，其复发和转移率较高。鉴定新的靶点可能有助于预测和治疗宫颈癌。NADPH 氧化酶 1（NOX1）基因介导的活性氧（ROS）的产生可诱导宫颈癌细胞的迁移和侵袭。肿瘤相关巨噬细胞（TAMs）在宫颈癌中发挥重要作用。肿瘤细胞衍生的外泌体介导肿瘤细胞与肿瘤微环境之间的信号转导。阐明参与调节 TAMs 的携带 NOX1 的外泌体的机制可能为宫颈癌的进展提供有价值的见解。
方法
从 UCSC 数据库下载泛癌的均匀标准化 mRNA 数据。使用 R 语言软件计算每种肿瘤类型肿瘤和相邻正常组织中 NOX1 的表达，并分析显著差异。从 GDC 下载所有使用 MuTect2 软件处理的 TCGA 样本的 SNP 数据集。细胞实验和动物肿瘤形成实验用于评估外泌体 NOX1 是否刺激 ROS 产生以促进宫颈癌中 TAM 的 M2 极化。
结果
NOX1 在泛癌中高表达且突变频率低。NOX1 的上调可能与宫颈癌组织中 M2 型巨噬细胞的浸润有关，并且通过刺激 ROS 产生促进宫颈癌细胞的恶性特征。外泌体 NOX1 通过刺激 ROS 产生促进 TAM 的 M2 极化。外泌体 NOX1 通过刺激 ROS 产生增强宫颈癌和体内 M2 极化的进展。
结论
外泌体 NOX1 通过刺激 ROS 产生促进 TAM M2 极化介导的宫颈癌进展。
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