2. Academic Validation
  3. Exosomal NOX1 promotes tumor-associated macrophage M2 polarization-mediated cancer progression by stimulating ROS production in cervical cancer: a preliminary study

Exosomal NOX1 promotes tumor-associated macrophage M2 polarization-mediated cancer progression by stimulating ROS production in cervical cancer: a preliminary study

  • Eur J Med Res. 2023 Sep 7;28(1):323. doi: 10.1186/s40001-023-01246-9.
Liying Gu # 1 2,  Chunyang Feng # 1 2,  Meng Li 3 4,  Zubei Hong 1 2,  Wen Di 5 6 7,  Lihua Qiu 8 9
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
  • 4 National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.
  • 5 Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. diwen163@163.com.
  • 6 Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. diwen163@163.com.
  • 7 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. diwen163@163.com.
  • 8 Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. lilyqiulh@126.com.
  • 9 Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. lilyqiulh@126.com.
  • # Contributed equally.
PMID: 37679792 DOI: 10.1186/s40001-023-01246-9
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.

Conclusion: Exosomal NOX1 promotes TAM M2 polarization-mediated Cancer progression through stimulating ROS production in cervical Cancer.

Keywords

Cervical cancer; Exosome; M2 polarization; NOX1; ROS; Tumor-associated macrophage.

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