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Function and pathway enrichment analysis for AP1S3-associated genes. (a–c) Enriched GO terms in biological process (BP), cell component (CC), and molecular function (MF). (d) Enriched KEGG pathways. The x-axis represents gene count; the y-axis represents GO term or enriched pathway. The color represents the P value.
Source publication
Introduction. Glioma is the widely occurring deadly neoplasm induced by glial cell canceration in the central nervous system, including the brain and spinal cord. The function of AP1S3 is special in numerous diseases, but its exact role in glioma remains unknown. Methods. Bioinformatics analysis was performed at the beginning. Based on TCGA databas...
Citations
... It was previously reported that the upregulation of AP-1 mediated by Hepatitis B virus-transfection promotes cell proliferation of HepG2, a cell line derived from hepatocellular carcinoma [14], and that μ1-adaptin could be one of prognostic markers for central nervous system metastasis of TNBC [15]. In addition, studies focusing on gene expression of AP1S3 that encodes σ1C revealed that it is highly expressed in TNBC, glioma, and pancreatic ductal adenocarcinoma (PDAC) [16][17][18], suggesting high expression of AP-1 complex in these cancers. We have recently reported that AP-1 containing γ1-adaptin could support cancer growth by maintaining cell surface expression of EGFR, and that γ1-adaptinpositive granular staining is often observed in tissues of hepatocellular carcinoma, non-small-cell lung carcinoma (NSCLC), and colorectal adenocarcinoma [13]. ...
... It has been shown that high expression of a subunit of AP-1, µ1A-adaptin, mediated by transfection of hepatitis B virus promotes cell proliferation in HepG2 cells [14], and that AP-1 (µ-adaptin) is required for the growth of plant cells in Arabidopsis [23]. Moreover, depletion of one of AP-1 subunit was found to inhibit proliferation of several cancer-derived cell lines, including glioma cell lines, SW1783 and U373 [18], a lung cancer cell line, H1975 [13], and a TNBC cell line, MDA-MB-231 [16]. Notably, a recent study of searching microRNA in TNBC identified AP1S3 as one of targets of miR-204-5p, and showed that low expression of miR-204-5p in MDA-MB-231 cells causes high expression of AP1S3 that encodes σ1C-adaptin, supporting proliferation, migration, and invasion of the cells [16]. ...
... Notably, a recent study of searching microRNA in TNBC identified AP1S3 as one of targets of miR-204-5p, and showed that low expression of miR-204-5p in MDA-MB-231 cells causes high expression of AP1S3 that encodes σ1C-adaptin, supporting proliferation, migration, and invasion of the cells [16]. This and similar reports further demonstrated that the AP1S3 transcript is highly expressed in TNBC, PDAC and glioma [16][17][18]. We also demonstrated in this study that depletion of γ1-adaptin in HER2-positive SK-BR-3 cells suppressed cell proliferation, migration, and invasion, and that there was a significant association between γ1-adaptin expression and the proliferation marker Ki-67 ( Fig. 4c and Table 1). ...
Background
γ1-Adaptin is a subunit of adaptor protein complex-1 (AP-1), which regulates intracellular transport between the trans-Golgi network (TGN) and endosomes. Since expression levels of AP-1 subunits have been reported to be associated with cell proliferation and cancer malignancy, we investigated the relationships between the immunohistochemical expression of γ1-adaptin and both clinicopathological factors and relapse-free survival (RFS) in breast cancer tissue.
Materials and methods
SK-BR-3 cell line depleted of γ1-adaptin was used for cell proliferation, migration, and invasion assay. Intracellular localization of γ1-adaptin was examined with immunohistochemistry (IHC) using an antibody against γ1-adaptin, and with double immunohistofluorescence (IHF) microscopy using markers for the TGN and endosome. γ1-Adaptin intensities in IHC samples from 199 primary breast cancer patients were quantified and assessed in relation to clinicopathological factors and RFS.
Results
Cell growth, migration, and invasion of SK-BR-3 cells were significantly suppressed by the depletion of γ1-adaptin. Although the staining patterns in the cancer tissues varied among cases by IHC, double IHF demonstrated that γ1-adaptin was mainly localized in EEA1-positive endosomes, but not in the TGN. γ1-Adaptin intensity was significantly higher in the tumor regions than in non-tumor regions. It was also higher in patients with Ki-67 (high), ER (–), PgR (–), and HER2 (+). Among subtypes of breast cancer, γ1-adaptin intensity was higher in HER2 than in luminal A or luminal B. The results of the survival analysis indicated that high γ1-adaptin intensity was significantly associated with worse RFS, and this association was also observed in group with ER (+), PgR (+), HER2 (–), Ki-67 (high), or luminal B. In addition, the Cox proportional hazards model showed that high γ1-adaptin intensity was an independent prognostic factor.
Conclusion
These results suggest that the endosomal expression of γ1-adaptin is positively correlated with breast cancer malignancy and could be a novel prognostic marker.
... Toda et al. [19] demonstrated that high AP1S3 expression level was significantly associated with poor prognosis in patients with breast cancer. In addition, AP1S3, overexpressed in glioma, promotes glioma progression [20]. However, the role of LINC00562-miR-4636-AP1S3 axis in glioma development remains unclear. ...
... AP1S3 is predicted by TargetScan to be a downstream target of miR-4636. Increased AP1S3 expression levels have been documented in breast cancer, glioma, and pancreatic ductal adenocarcinoma [19,20,27]. AP1S3 is targeted by miR-204-5p, and miR-204-5p represses breast cancer cell migration and invasion by depleting AP1S3 [19]. ...
... AP1S3 is targeted by miR-204-5p, and miR-204-5p represses breast cancer cell migration and invasion by depleting AP1S3 [19]. In addition, AP1S3 depletion also restrained glioma cell proliferation, migration, and invasion [20]. Following these results, we knocked down AP1S3 expression in GC cells and demonstrated that cell proliferation, colony formation, migration, and survival were repressed. ...
Dysregulation of certain long non-coding RNAs may facilitate tumor initiation and progression. However, numerous carcinogenesis-related long non-coding RNAs have not been characterized. The goal of this study was to elucidate the role of LINC00562 in gastric cancer (GC). The expression of LINC00562 was analyzed using real-time quantitative PCR and Western blotting. The proliferative capacity of GC cells was determined using Cell Counting Kit-8 and colony-formation assays. The migration of GC cells were evaluated using wound-healing assays. The apoptosis of GC cells was assessed by measuring the expression levels of apoptosis-related proteins (Bax and Bcl-2). Xenograft models in nude mice were constructed for in vivo functional analysis of LINC00562. The binding relationship between miR-4636 and LINC00562 or adaptor protein complex 1 sigma 3 (AP1S3), obtained from public databases, was confirmed using dual-luciferase and RNA-binding protein immunoprecipitation experiments. LINC00562 was expressed in GC cells at high levels. Knockdown of LINC00562 repressed GC cell growth and migration, promoted apoptosis in vitro, and inhibited tumor growth in nude mouse models. LINC00562 directly targeted miR-4636, and miR-4636 depletion restored the GC cell behavior inhibited by LINC00562 absence. AP1S3, an oncogene, binds to miR-4636. MiR-4636 downregulation increased AP1S3 level, restoring GC cell malignant behaviors inhibited by AP1S3 downregulation. Thus, LINC00562 exerts carcinogenic effects on GC development by targeting miR-4636-mediated AP1S3 signaling.
Background
Glioblastoma multiforme (GBM) is a type of fast-growing brain glioma associated with a very poor prognosis. This study aims to identify key genes whose expression is associated with the overall survival (OS) in patients with GBM.
Methods
A systematic review was performed using PubMed, Scopus, Cochrane, and Web of Science up to Journey 2024. Two researchers independently extracted the data and assessed the study quality according to the New Castle Ottawa scale (NOS). The genes whose expression was found to be associated with survival were identified and considered in a subsequent bioinformatic study. The products of these genes were also analyzed considering protein-protein interaction (PPI) relationship analysis using STRING. Additionally, the most important genes associated with GBM patients’ survival were also identified using the Cytoscape 3.9.0 software. For final validation, GEPIA and CGGA (mRNAseq_325 and mRNAseq_693) databases were used to conduct OS analyses. Gene set enrichment analysis was performed with GO Biological Process 2023.
Results
From an initial search of 4104 articles, 255 studies were included from 24 countries. Studies described 613 unique genes whose mRNAs were significantly associated with OS in GBM patients, of which 107 were described in 2 or more studies. Based on the NOS, 131 studies were of high quality, while 124 were considered as low-quality studies. According to the PPI network, 31 key target genes were identified. Pathway analysis revealed five hub genes (IL6, NOTCH1, TGFB1, EGFR, and KDR). However, in the validation study, only, the FN1 gene was significant in three cohorts.
Conclusion
We successfully identified the most important 31 genes whose products may be considered as potential prognosis biomarkers as well as candidate target genes for innovative therapy of GBM tumors.
Adenosine-to-inosine RNA editing (ATIRE) is a common form of ribonucleic acid (RNA) editing, which has highlighted the importance of ATIRE in tumors. However, its role in bladder cancer (BLCA) remains poorly understood. To study ATIRE impact on BLCA patient prognosis, we obtained ATIRE, gene expression, and clinical data from the Cancer Genome Atlas (TCGA) database for 251 patients, randomly dividing them into training and testing groups. Univariate proportional hazards model (COX) regression identified prognosis-associated ATIRE loci, while the least absolute shrinkage and selection operator (LASSO) selected final loci to construct prognostic models and generate ATIRE scores. We developed a nomogram to predict BLCA patients' overall survival (OS) and analyzed the effect of ATIRE editing levels on host gene expression. We also compared immune cell infiltration and drug treatment between patients with high and low ATIRE scores. The ATIRE prognostic prediction model was constructed using ten ATIRE loci that are closely associated with BLCA survival. Patients with high ATIRE scores showed significantly worse OS than those with low ATIRE scores. Furthermore, the nomogram, which incorporates the ATIRE score, can better predict the prognosis of patients. Multiple functional and pathway changes associated with immune responses, as well as significant differences in immune cell infiltration levels and response to drug therapy were observed between patients with high and low ATIRE scores. This study represented the first comprehensive analysis of the role of ATIRE events in BLCA patient prognosis and provided new insights into potential prognostic markers for BLCA research.
