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Abstract：
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.
CONCLUSIONS: Exosomal NOX1 promotes TAM M2 polarization-mediated cancer progression through stimulating ROS production in 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.
CONCLUSIONS: Exosomal NOX1 promotes TAM M2 polarization-mediated cancer progression through stimulating ROS production in cervical cancer.
摘要：
背景：宫颈癌是女性癌症死亡的第四大主要原因，2020年全球估计有604,000例新病例和342,000例死亡，复发和转移率很高。新靶点的鉴定有助于宫颈癌的预测和治疗。NADPH氧化酶1（NOX1）基因介导的活性氧（ROS）的产生可以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。肿瘤细胞来源的外泌体介导肿瘤和肿瘤微环境之间的信号转导。阐明携带NOX1的外泌体参与TAM调节的机制可能为宫颈癌的进展提供有价值的见解。
方法：下载UCSC数据库中泛癌的一致标准化mRNA数据。使用R语言软件计算每种肿瘤类型的肿瘤和癌旁正常组织中NOX1的表达，并分析差异的统计学意义。下载使用来自GDC的MuTect2软件处理的所有TCGA样品的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TAM的M2极化。
结果：NOX1在泛癌中高表达，突变频率低。NOX1上调可能与宫颈癌组织中M2型巨噬细胞浸润有关,NOX1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M2极化。外泌体NOX1通过刺激ROS产生增强体内宫颈癌和M2极化的进展。
结论：外泌体NOX1通过刺激宫颈癌中的ROS产生促进TAMM2极化介导的癌症进展。
方法：下载UCSC数据库中泛癌的一致标准化mRNA数据。使用R语言软件计算每种肿瘤类型的肿瘤和癌旁正常组织中NOX1的表达，并分析差异的统计学意义。下载使用来自GDC的MuTect2软件处理的所有TCGA样品的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TAM的M2极化。
结果：NOX1在泛癌中高表达，突变频率低。NOX1上调可能与宫颈癌组织中M2型巨噬细胞浸润有关,NOX1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M2极化。外泌体NOX1通过刺激ROS产生增强体内宫颈癌和M2极化的进展。
结论：外泌体NOX1通过刺激宫颈癌中的ROS产生促进TAMM2极化介导的癌症进展。
