Multi-omics approaches establishing histone modification based prognostic model in glioma patients and further verification of the carcinogenesis mechanism.

Glioblastoma (GBM) emerges as the most common malignant brain tumor. Histone modifications, as an epigenetic regulatory mechanism of gene expression, are closely associated with malignant tumors. Gene set related to histone modification was extracted from the MSigDB database, and scored by the function of AddModuleScore. Pearson correlation analysis was utilized using the "rcorr" function of "Hmisc" R package. Genes were screened out using the LASSO Cox analysis. TCGA-GBM and CGGA_array_301 cohorts were employed for constructing model and validation. We calculated immune infiltration scores using microenvironment cell populations counter (MCPcounter), single-sample gene set enrichment analysis (ssGSEA), and xCell algorithms. U87-MG and CHG-5 cell lines were utilized to evaluate expression level of TMEM176A by western blot (WB). Transwell, EDU, colony formation analysis (CFA), and CKK-8 assays were conducted to investigate cell proliferation and migration rate. The malignant cells in GBM patients exhibited notable activation in the TGF-ß and hypoxia pathway. Histone modifications were associated with adhesion and neuron development in GBM. We identified a model with five significant genes, namely NBEAL1, AEBP1, TMEM176A, FASTK, and CD81, with prognostic efficacy. Additionally, we observed increased infiltration of T cells and CD8+ T cells in the high-risk (HR) group. 5-Fluorouracil_1073 and Taselisib_1561 were predicted as potential treatment options for GBM patients, while ABT737_1910 and Wnt_C59-1622 exhibited superior response in GBM patients of the HR group. A spike in the TP53 mutation rate was observed in the HR group. TMEM176A played a role in regulating cell proliferation and migration in vitro. We presented a novel prognostic model for patients with GBM, based on histone modification-related genes. In addition, we identified the crucial role of the TMEM176A in the regulation of GBM carcinogenic phenotypes for the first time.

Application of Bioinformatics Analysis to Identify Important Pathways and Hub Genes in Ovarian Cancer Affected by WT1.

Wilms tumor gene (WT1) is used as a marker for the diagnosis and prognosis of ovarian cancer. However, the molecular mechanisms involving WT1 in ovarian cancer require further study. Herein, we used bioinformatics and other methods to identify important pathways and hub genes in ovarian cancer affected by WT1. The results showed that WT1 is highly expressed in ovarian cancer and is closely related to the overall survival and progression-free survival (PFS) of ovarian cancer. In ovarian cancer cell line SKOV3, WT1 downregulation increased the mRNA expression of 638 genes and decreased the mRNA expression of 512 genes, which were enriched in the FoxO, AMPK, and the Hippo signaling pathways. The STRING online tool and Cytoscape software were used to construct a Protein-protein interaction (PPI) network and for Module analysis, and 18 differentially expressed genes (DEGs) were selected. Kaplan-Meier plotter analysis revealed that 16 of 18 genes were related to prognosis. Analysis of GEPIA datasets indicated that 7 of 16 genes were differentially expressed in ovarian cancer tissues and in normal tissues. The expression of IGFBP1 and FBN1 genes increased significantly after WT1 interference, while the expression of the SERPINA1 gene decreased significantly. The correlation between WT1 expression and that of these three genes was consistent with that of ovarian cancer tissues and normal tissues. According to the GeneMANIA online website analysis, there were complex interactions between WT1, IGFBP1, FBN1, SERPINA1, and 20 other genes. In conclusion, we have identified important signaling pathways involving WT1 that affect ovarian cancer, and distinguished three differentially expressed genes regulated by WT1 associated with the prognosis of ovarian cancer. Our findings provide evidence outlining mechanisms involving WT1 gene expression in ovarian cancer and provides a rational for novel treatment of ovarian cancer.

Asynchronous responses of soil microbial community and understory plant community to simulated nitrogen deposition in a subtropical forest.

Atmospheric nitrogen (N) deposition greatly affects ecosystem processes and properties. However, few studies have simultaneously examined the responses of both the above- and belowground communities to N deposition. Here, we investigated the effects of 8 years of simulated N deposition on soil microbial communities and plant diversity in a subtropical forest. The quantities of experimental N added (g of N m(-2) year(-1)) and treatment codes were 0 (N0, control), 6 (N1), 12 (N2), and 24 (N3). Phospholipid fatty acids (PLFAs) analysis was used to characterize the soil microbial community while plant diversity and coverage were determined in the permanent field plots. Microbial abundance was reduced by the N3 treatment, and plant species richness and coverage were reduced by both N2 and N3 treatments. Declines in plant species richness were associated with decreased abundance of arbuscular mycorrhizal fungi, increased bacterial stress index, and reduced soil pH. The plasticity of soil microbial community would be more related to the different responses among treatments when compared with plant community. These results indicate that long-term N deposition has greater effects on the understory plant community than on the soil microbial community and different conservation strategies should be considered.