ABSTRACT
Objective: Gastric cancer has a poor prognosis and high mortality. Cuproptosis, a novel programmed cell death, is rarely studied in gastric cancer. Studying the mechanism of cuproptosis in gastric cancer is conducive to the development of new drugs, improving the prognosis of patients and reducing the burden of disease. Methods: The TCGA database was used to obtain transcriptome data from gastric cancer tissues and adjacent tissues. GSE66229 was used for external verification. Overlapping genes were obtained by crossing the genes obtained by differential analysis with those related to copper death. Eight characteristic genes were obtained by three dimensionality reduction methods: lasso, SVM, and random forest. ROC and nomogram were used to estimate the diagnostic efficacy of characteristic genes. The CIBERSORT method was used to assess immune infiltration. ConsensusClusterPlus was used for subtype classification. Discovery Studio software conducts molecular docking between drugs and target proteins. Results: We have established the early diagnosis model of eight characteristic genes (ENTPD3, PDZD4, CNN1, GTPBP4, FPGS, UTP25, CENPW, and FAM111A) for gastric cancer. The results are validated by internal and external data, and the predictive power is good. The subtype classification and immune type analysis of gastric cancer samples were performed based on the consensus clustering method. We identified C2 as an immune subtype and C1 as a non-immune subtype. Small molecule drug targeting based on genes associated with cuproptosis predicts potential therapeutics for gastric cancer. Molecular docking revealed multiple forces between Dasatinib and CNN1. Conclusion: The candidate drug Dasatinib may be effective in treating gastric cancer by affecting the expression of the cuproptosis signature gene.
ABSTRACT
Aim: This study investigated the effect of FoxM1 on the biological behavior of neuroblastoma (NB) cells in vitro and the association between FoxM1 and PI3K/AKT pathways in NB cell lines. Materials and methods: Recombinant plasmid pcDNA3.1 (+)-FoxM1 and FoxM1-specific small interfering RNA (siRNA) were transfected into IMR-32 cells by liposome transfection. The expression of FoxM1, AKT and PI3K were determined by qRT-PCR and western blotting. The effect of FoxM1 and PI3K/AKT pathways on the cell cycles and apoptosis were analyzed by flow cytometry. Cell viability and proliferation ability were assessed by CCK8 and colony formation assay. Results: Knockdown of FoxM1 promoted NB cell apoptosis and G1-phase cell cycle arrest significantly, increased the expression of apoptosis-related proteins, and suppressed the phospho-activation of PI3K and AKT. Over-expression of FoxM1 had the opposite effects. Conclusion: FoxM1 knockdown inhibited NB cell proliferation and induced apoptosis through inhibiting activation of PI3K and AKT.
Subject(s)
Forkhead Box Protein M1 , Neuroblastoma , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Forkhead Box Protein M1/genetics , Forkhead Box Protein M1/metabolism , Humans , Neuroblastoma/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
The aim of this study was to investigate the therapeutic effects and underlying mechanism of tetramethylpyrazine (TMP) on lung development using a rat model of congenital diaphragmatic hernia (CDH). Nitrofen was used to induce CDH. Pregnant rats were divided into three groups: control, CDH, and CDH+TMP. In the CDH and CDH+TMP, fetuses only with left diaphragmatic hernias were chosen for analysis. Lung and body weight were recorded and lung histologic evaluations, image analysis, and western blot analysis of YAP, p-YAP and LATS1 were performed after lung processing. A markedly abnormal structure was observed, as evidenced by pulmonary hypoplasia and vascular remodeling, in the CHD. These abnormalities were improved in the CDH+TMP. There were significant differences between the CHD and CHD+TMP in percentage of medial wall thickness, arteriole muscularization, radial alveolar counts, AA%, and alveolar septal thickness. YAP expression was markedly increased in the CHD compared to the controls, which was not affected by antenatal TMP administration. However, prenatal TMP intervention significantly increased expression of LATS1 and phosphorylation of YAP in the CDH fetuses. Our results demonstrate that antenatal TMP administration improved vascular remodeling and promoted lung development in a rat model of CHD, potentially through increasing expression of LATS1 and phosphorylation of YAP.