ABSTRACT
Cell cycle dysregulation leading to uncontrolled growth is a primary characteristic of malignancy. GSG2, a mitosis-related kinase, affects the normal cell cycle by interfering with the normal dissociation of centromere cohesion, and its overexpression has been shown to play an important role in cancer cells. Here, we investigated the function of GSG2 as a tumor promoter in endometrial carcinoma and its relationship with the immunological microenvironment. We used immunohistochemistry to identify a correlation between the development and prognosis of GSG2 and endometrial cancer. Cell and animal experiments confirmed that GSG2 has a protumorigenic phenotype in endometrial cancer cell lines. Furthermore, using GeneChip analysis and a tumor-immune coculture model, we observed a link between GSG2 expression and the composition of the immune microenvironment. Therefore, we concluded that the activation of the PI3K/AKT pathway by GSG2 may impact DNA repair, disrupt the cell cycle, and regulate the immune response, all of which could increase the ability of EC cells to proliferate malignantly. Consequently, it is anticipated that GSG2 will be a viable therapeutic target in endometrial carcinoma.
Subject(s)
B7-H1 Antigen , Endometrial Neoplasms , Phosphatidylinositol 3-Kinases , Programmed Cell Death 1 Receptor , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Female , Humans , Mice , Aurora Kinase B , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Cell Line, Tumor , Disease Progression , Endometrial Neoplasms/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/immunology , Endometrial Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Mice, Inbred BALB C , Mice, Nude , Mitogen-Activated Protein Kinase Kinases , Phosphatidylinositol 3-Kinases/metabolism , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/genetics , Proto-Oncogene Proteins c-akt/metabolism , Tumor Microenvironment/immunologyABSTRACT
Organoids faithfully replicate the morphological structure, physiological functions, stable phenotype of the source tissue. Recent research indicates that bacteria can significantly influence the initiation, advancement, and treatment of tumors. This article provides a comprehensive review of the applications of organoid technology in tumor research, the relationship between bacteria and the genesis and development of tumors, and the exploration of the impact of bacteria on tumors and their applications in research.
Subject(s)
Neoplasms , Organoids , Organoids/pathology , Organoids/microbiology , Humans , Neoplasms/pathology , Neoplasms/microbiology , Bacteria , Models, Biological , AnimalsABSTRACT
OBJECTIVES: The aim of this study was to characterize cervical microbiome feature of reproductive-age women in the progression of squamous intraepithelial lesions (SIL) to cervical cancer. METHODS: We characterized the 16S rDNA cervical mucus microbiome in 94 participants (age from 18 to 52), including 13 cervical cancer (CA), 31 high-grade SIL (HSIL), 10 low-grade SIL (LSIL), 12 HPV-infected (NH) patients and 28 healthy controls (NN). Alpha (within sample) diversity was examined by Shannon and Simpson index, while Beta (between sample) diversity by principle coordinate analysis (PCoA) of weighted Unifrac distances. Relative abundance of microbial taxa was compared using Linear Discriminant Analysis Effect Size (LEfSe). Co-occurrence analysis was performed to identify correlation among marker genera, and Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) to explore functional features and pathways of cervical microbiota. RESULTS: Alpha diversity(p < 0.05) was higher in severer cervical pathology with lower relative abundance of Lactobacillus as well as higher of anaerobes. Beta diversity (p < 0.01) was significantly different. Marker genera were identified including Porphyromonas, Prevotella and Campylobacter of CA and Sneathia of HSIL. The correlation of differential functional pathways with Prevotella was opposite to that with Lactobacillus. CONCLUSION: Our study suggests differences in cervical microbiota diversity and relative abundance of reproductive-age females in different stages of cervical carcinogenesis. Marker genera might participate in the lesion progression and will be helpful for diagnosis, prevention and treatment. These findings may lead the way to further study of the cervical microbiome in development of cervical cancer.
