Purpose: Previous studies have shown that non-SMC condensin I complex subunit G (NCAPG) overexpression is correlated to poor prognosis of multiple cancer types. Herein, we explored the underlying mechanism of NCAPG-mediated cardia adenocarcinoma (CA) proliferation and cell cycle regulation. Methods: The protein profiling technology was used to analyze the gene expression in 20 CA and adjacent tissue samples. Differential genes were identified by bioinformatic analysis. Western blot and qRT-PCR-based analysis assessed the NCAPG expression levels in multiple CA cell lines. CA cell lines, SGC-7901 and AGS, were transfected with Lip 2000, and stably transfected cell lines were screened for NCAPG overexpression and downregulation. MTT and clone formation assays were employed to detect cell proliferation, and cell cycle phases were analyzed using flow cytometry. Western blot was performed to determine the NCAPG gene expression levels. Finally, we studied the tumorigenic effects of NCAPG in the mouse model and validated the cell experiment results using immunohistochemistry. Results: A significant overexpression of NCAPG was found in CA tissues and CA cell lines. The outcomes of MTT and clone formation assays showed that NCAPG upregulation promoted cell proliferation. The outcomes of these analyses were further validated using nude mice as an in vivo tumor model. As per the outcome of Western blot and flow cytometry analysis, NCAPG regulated the G1 phase through the cyclins (CDK4, CDK6, and cyclin D1) overexpression and cell cycle inhibitors (P21 and P27) downregulation. Overexpressed NCAPG and silenced NCAPG, both in vitro and in vivo, resulted in abnormal activation of the PI3K/AKT signaling pathway in CA cells. We observed that NCAPG overexpression increased the levels of phosphorylated PI3K, AKT, and GSK3β; however, their total protein levels remained unchanged in CA cells. Conclusion: As a CA oncogene, NCAPG promoted cell proliferation and regulated cell cycle through PI3K/AKT signaling pathway activation.

Background: Cancer cells evade oxidative stress through the MutT homologue-1 (MTH1), a member of the Nudix family. MTH1 maintains genome integrity and the viability of tumor cells. A new class of MTH1 inhibitors have attracted interest as anticancer agents, but their mechanisms of action remain poorly characterized. In this study, the authors evaluated the anticancer effects of the MTH1 inhibitor TH287 on gastric cancer (GCa) cells. Materials and Methods: BGC-823 and SGC-7901 cells were treated with TH287 and CCK-8, and colony-forming assays were performed. Cell migration was assessed through Transwell and scratch assays. Apoptotic status was measured via flow cytometry and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) staining. Cell cycle status was assessed by propidium iodide (PI) staining. The expression of PI3K/AKT signaling-related proteins was verified by western blotting. Results: TH287 inhibited cell viability, reduced cell proliferation, inhibited apoptosis, induced G2/M arrest, and suppressed cell migration. A loss of mitochondrial membrane potential and reduced Bcl-2/Bax expression were also observed in TH287-treated cells. These effects were mediated through the inhibition of pro-oncogenic PI3K/AKT signaling. Conclusions: These findings indicate that the MTH1 inhibitor TH287 mediates an array of anticancer effects in GCa cells through its effects on mitochondrial function and PI3K/AKT signaling. Collectively, these data highlight the promise of TH287 as a novel therapeutic option for GCa cells.

Background: Glutathione peroxidase 8 (GPX8) has previously been shown to play a role in Keshan disease. In the present study. we explored the prognostic relevance of GPX8 expression in patients with gastric cancer (GC) based upon The Cancer Genome Atlas (TCGA) data. Material/Methods: We assessed the relationship between the expression of GPX8 and clinicopathological findings in GC patients via logistic regression analyses, Kruskal-Wallis tests, and Wilcoxon signed-rank tests. We further assessed the prognostic relevance of specific variables using Kaplan-Meier and Cox regression analyses. We lastly conducted gene set enrichment analyses (GSEA). Results: We detected a significant association between elevated GPX8 levels and more advanced GC tumor stage (OR=5.92 for I vs. IV), as well as more advanced T (OR=22.91 for T1 vs. T4) and N classification (OR=1.82 for N0 vs. N3). We found worse prognosis in patients expressing high levels of GPX8 relative to those with lower expression of this gene (P=0.021). In a univariate analysis. we found high GPX8 expression was strongly correlated with worse OS (hazard ratio [FIR]: 1.05; 95% confidence interval [CI]: 1.01-1.08; P=0.018), and multivariate analysis confirmed that GPX8 expression independently predicts GC patient OS (HR: 1.04; CI: 1.00-1.08, P=0.041). GSEA revealed that elevated GPX8 expression was associated with enrichment of pathways consistent with MAPK signaling, JAK/STAT signaling, TGF-beta signaling, melanoma, and basal cell carcinoma. Conclusions: The expression of GPX8 may have prognostic relevance, being positively associated with worse OS in GC patients.

Background. Nonstructural maintenance of non-SMC condensin I complex subunit G (NCAPG) exerts critical effects on cancer progression. However, its biological roles in tumorigenesis and metastasis remain unclear. Thus, we aimed to assess the prognostic utility of NCAPG in stomach adenocarcinoma (STAD) and its potential as a tumor biomarker. Methods. Pan-cancer expression profile dataset from public databases and corresponding clinical information were extracted. Single-sample gene set enrichment analysis (ssGSEA) was performed for the evaluation of immune correlations pan-cancer. Subsequently, we focused on STAD and evaluated the methylation profiles, copy number variants (CNVs), and single nucleotide variants (SNVs). Immune features were analyzed between high and low NCAPG expression groups. Differential analysis was performed between high and low expression groups to identify differentially expressed genes (DEGs). Prognostic DEGs were screened by univariate analysis, and an NCAPG-based risk model was constructed based on the prognostic DEGs and LASSO analysis. Results. NCAPG expression in STAD was significantly and positively correlated with four immune checkpoints, namely, CTLA4, PDCD1, LAG3, and CD276, but was negatively correlated with the infiltration of most immune cells. High and low NCAPG expression groups had differential overall survival, tumor mutation burden, and differential enrichment of therapeutic-related pathways. An immune risk scoring model related to NCAPG expression and immune score was constructed which showed a favorable performance in predicting STAD prognosis as well as predicting the response to immunotherapy. In addition, we found a higher mRNA stemness index (mRNAsi) in the high-risk group and a positive correlation between NCAPG expression and mRNAsi. Conclusion. NCAPG was suggested to be involved in the regulation of tumor microenvironment in STAD. High NCAPG expression was related to high tumor stemness and good prognosis. The immune risk model had a potential to predict STAD prognosis and help directing therapeutic treatment.

Background. Gastric cancer (GC) is a highly prevalent tumor type. The dysregulated expression of melanoma deficiency factor 2 (AIM2) has been observed in a range of tumor types. Herein, we explore the role of AIM2 in the regulation of GC progression. Methods. Gastric cancer cells BGC-823 and MGC-803 in logarithmic growth phase were divided into blank group (control), Control group (NC) and SH-AIM2 group, respectively. Control group and SH-AIM2 group were transfected with AIM2 NC and SH-AIM2, respectively. Nude mice were divided into blank group (control) and SH-AIM2 group, and the treatment methods were the same as above. Differential AIM2 expression in GC tissues was assessed via bioinformatics analyses, after which western blotting was used for analyzing the AIM2 levels in tumor and paracancerous tissues from five stomach cancer patients. In addition, qPCR and protein imprinting were used to assess AIM2 expression levels in GCcells, and AIM2 knockdown was conducted in MGC-803 and BGC-823cells, after which colony formation and EdU incorporation assay were utilized to assess cell proliferation. The oncogenic role of AIM2 was then assessed in mice and validated through immunohistochemical analyses. Results. GC tissues and cell lines exhibited marked AIM2 overexpression. AIM2 knockdown significantly impaired GC cell proliferation and migration, as confirmed through in vitro assays. In vivo experiments showed that both the increment ability and invasion and migration ability of AIM2 knockdown group were significantly lower than that of control and NC the change of AIM2 protein level would affect the change of MAPK pathway related protein level. Conclusions. AIM2 knockdown markedly suppresses the proliferation, migration, as well as invasion of GC cells via the inhibition of MAPK signaling, thereby slowing tumor progression. Overall, these results suggest that further analyses of AIM2 may offer clinically valuable insights that can aid in the treatment of human GC.