POU3F4, a transcription factor (TF), has been proved to be critical regulator of inner ear and pancreas development and neurogenesis. Despite growing evidence confirming the indispensable role of POU3F4 in carcinogenesis of specific cancers, the pan-cancer assessment of POU3F4 remains scanty. As a result, we aimed at studying the prognostic value of POU3F4 in thirty-three cancers and to study the underlying function in immunity. On the grounds of data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression and Gene Set Cancer Analysis, we made use of numerous bioinformatics ways to study the prospective carcinogenic effects of POU3F4, DNA methylation, RNA methylation, tumor mutation burden (TMB), mismatch repair (MMR) gene, microsatellite instability (MSI), POU3F4-prognosis interrelation, and immune cell infiltration (ICI) in discrepant tumors. The analysis yielded that the POU3F4 expression was at a low rate in most cancers, while it was higher in breast invasive carcinoma, glioblastoma multiforme, liver hepatocellular carcinoma, and thyroid carcinoma. Additionally, POU3F4 had a link with the prognosis of discrepant cancers, either positively or negatively. Expression of POU3F4 showed relevance to MSI (4 cancer types) and TMB (6 cancer types), and exhibited striking relevance to DNA methylation (13 cancer types) and RNA methylation (most cancers). Additionally, its expression was associated with tumor immune microenvironment, immune-related genes, ICI and drug resistance in different cancers. In vitro experiments had shown that POU3F4 could increase cell viability, proliferation and migration of glioma cells. Our research reveals that concerning the indispensable function in carcinogenesis and tumor immunity, POU3F4 is deemed as a prognostic hallmark in discrepant malignancies.
Background Immunosuppression is a key feature of cancer, promoting tumor growth and progression. Regulatory T cells (Tregs) are a specialized subset of T lymphocytes that mediate immunosuppression in cancer. However, the role of Treg-related genes in ovarian cancer (OC) remains largely unexplored.Methods To identify marker genes related to Tregs in OC, we utilized scRNA-seq analysis. Treg scores were then constructed using single-sample gene set enrichment analysis (ssGSEA) based on these markers. To identify gene modules with the strongest correlation with Treg scores in bulk RNA-seq data, we employed the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm. Multiple machine learning algorithms were then used to construct risk models with superior predictive performance, which were validated using external independent datasets. A risk score was developed for each OC sample based on the optimal model to evaluate differences in prognosis, immune infiltration, pathway activity, and immunotherapy between high and low-risk groups.Results We identified 365 genes regulating Treg activity using the WGCNA algorithm, and found that 70 of these genes were associated with the prognosis of OC based on univariate cox analysis. Using a combination of the Random Survival Forest (RSF) and Lasso algorithms, we constructed a risk model with the highest c-index based on the assigned risk scores. The model's performance was validated using four external datasets. Our analysis revealed that the low-risk group had a better prognosis, more immune cell infiltration, higher immune checkpoint expression, and significant differences in pathway enrichment and immunotherapy efficacy between the different risk groups.Conclusion Our findings provide new insights into the role of Treg cells in the development and progression of OC and highlight the potential for developing novel Treg-targeted therapies for the treatment of this disease.
The transcription factor Brn4 exhibits vital roles in the embryonic development of the neural tube, inner ear, pancreas islet, and neural stem cell differentiation. Our previous studies have shown that Brn4 promotes neuronal differentiation of hippocampal neural stem cells (NSCs). However, its mechanism is still unclear. Here, starting from the overlapping genes between RNA-seq and ChIP-seq results, we explored the downstream target genes that mediate Brn4-induced hippocampal neurogenesis. There were 16 genes at the intersection of RNA-seq and ChIP-seq, among which the Lama2 and Samsn1 levels can be upregulated by Brn4, and the combination between their promoters and Brn4 was further determined using ChIP and dual luciferase reporter gene assays. EdU incorporation, cell cycle analysis, and CCK-8 assay indicated that Lama2 and Samsn1 mediated the inhibitory effect of Brn4 on the proliferation of hippocampal NSCs. Immunofluorescence staining, RT-qPCR, and Western blot suggested that Lama2 and Samsn1 mediated the promoting effect of Brn4 on the differentiation of hippocampal NSCs into neurons. In conclusion, our study demonstrates that Brn4 binds to the promoters of Lama2 and Samsn1, and they partially mediate the regulation of Brn4 on the proliferation inhibition and neuronal differentiation promotion of hippocampal NSCs.
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