Anoctamin 5 regulates the cell cycle and affects prognosis in gastric cancer
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PROVIDER: PRJNA783862 | ENA |
REPOSITORIES: ENA
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Project description:BackgroundAnoctamin 5 (ANO5)/transmembrane protein 16E belongs to the ANO/ transmembrane protein 16 anion channel family. ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid scrambling and regulate other membrane proteins in numerous cell types. Previous studies have elucidated the roles and mechanisms of ANO5 activation in various cancer types. However, it remains unclear whether ANO5 acts as a plasma membrane chloride channel, and its expression and functions in gastric cancer (GC) have not been investigated.AimTo examine the role of ANO5 in the regulation of tumor progression and clinicopathological significance of its expression in GC.MethodsKnockdown experiments using ANO5 small interfering RNA were conducted in human GC cell lines, and changes in cell proliferation, cell cycle progression, apoptosis, and cellular movement were assessed. The gene expression profiles of GC cells were investigated following ANO5 silencing by microarray analysis. Immunohistochemical staining of ANO5 was performed on 195 primary tumor samples obtained from patients with GC who underwent curative gastrectomy between 2011 and 2013 at our department.ResultsReverse transcription-quantitative polymerase chain reaction (PCR) and western blotting demonstrated high ANO5 mRNA and protein expression, respectively, in NUGC4 and MKN45 cells. In these cells, ANO5 silencing inhibited cell proliferation and induced apoptosis. In addition, the knockdown of ANO5 inhibited G1-S phase progression, invasion, and migration. The results of the microarray analysis revealed changes in the expression levels of several cyclin-associated genes, such as CDKN1A, CDK2/4/6, CCNE2, and E2F1, in ANO5-depleted NUGC4 cells. The expression of these genes was verified using reverse transcription-quantitative PCR. Immunohistochemical staining revealed that high ANO5 expression levels were associated with a poor prognosis. Multivariate analysis identified high ANO5 expression as an independent prognostic factor for 5-year survival in patients with GC (P = 0.0457).ConclusionANO5 regulates the cell cycle progression by regulating the expression of cyclin-associated genes and affects the prognosis of patients with GC. These results may provide insights into the role of ANO5 as a key mediator in tumor progression and/or promising prognostic biomarker for GC.
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Project description:Anoctamin 5 as a key mediator in tumor progression, it may being a promising prognostic biomarker for a novel therapeutic target of GC.
2021-11-29 | GSE189601 | GEO
Project description:Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer
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Project description:Gastric cancer poses a significant threat at advanced stages, with the identification of molecular signatures for prognosis and targeted treatment remaining crucial yet challenging. This study investigates the under-characterized gastric cancer glycocalyx, revealing glycan signatures linked to cancer aggressiveness through high-throughput N-glycome analysis. Our findings show that aggressive tumors with poorer prognoses are enriched with trimmed paucimannosidic N-glycans. Lectin immunoblotting confirmed the disease-specific nature of these glycans, showing increased expression with cancer progression. Furthermore, TCGA analysis of over 400 cases revealed a correlation between key glycosyltransferase expression, associated with paucimannose biosynthesis, and poor prognosis, providing a potential molecular basis for these observations. Paucimannose N-glycans were predominantly found in intracellular ribosomal proteins challenging classical links with the plasma membrane proteome, though notable membrane proteins like CEACAM6 and MMP9 were identified. MMP9 demonstrated limited expression in healthy tissues, increasing with disease stage and grade. Tumors expressing MMP9 and paucimannosidic glycans also exhibited the worst prognosis. This work advances our understanding of gastric cancer glycome, highlighting the clinical context for paucimannosidic N-glycans and its underlying glycoproteome, providing potential targets for more precise therapeutic approaches.
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2018-02-06 | GSE110078 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is in the highlights as a significant role in tumor progression and invasion. Snail was known as the one of regulators of EMT in various malignant tumors. The aim of this study was to investigate the effect of Snail on invasiveness/migratory ability of gastric cancer cell lines and clinicopathological and prognostic significance of Snail over-expression using immunohistochemistry in tissue microarray of 314 gastric adenocarcinomas (GC). Differential gene expression in Snail over-expressed GC was investigated using cDNA microarray analysis. Silencing of Snail by ShRNA induced decreased of invasion, migration of gastric cancer cell lines. In contrast, over-expression of Snail induced increased invasiveness and migratory ability of gastric cancer cell lines in accordance increase of VEGF and MMP11. Furthermore, the over-expression of Snail (?75% nuclear staining of Snail) was significantly associated with tumor progression (p<0.0001), lymph node metastases (p=0.002), lymphovascular invasion (p=0.002), and perineural invasion (p=0.002) in 314 GC patient. Snail over-expression was also associated with poor prognosis (shorter survival) in GC patients (p=0.023). cDNA microarray revealed 213 differential expressed genes in Snail over-expressed GC tissues, including genes related to metastasis, invasion. Based on above results, it was suggested that Snail plays a significant role in invasiveness/migratory ability of GCs. In addition, Snail might be used to predictive biomarker for evaluation of prognosis or aggressiveness in GCs. 48 primary gastric adenocarcinoma fresh frozen tissues were used for microarray. All the tissues were obtained after curative resection after pathologic confirm at Pusan National University Hospital (PNUH, Busan, Korea) and Cheonnam University Hospital (CNUH, Cheonnam, Korea). Microarray experiment and data analysis were done at Cancer research institute, PNUH, Busan, Korea.
2012-05-17 | E-GEOD-38024 | biostudies-arrayexpress
Project description:Reversible acetylation of HDAC8 regulates cell cycle
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Project description:TRPS1 is aberrantly expressed in a variety of tumors, including breast, prostate, and gastric cancers, and is strongly associated with tumorigenesis or prognosis. However, the role of TRPS1 in high grade serous ovarian carcinoma (HGSC) is unknown. We investigated the relationship between TRPS1 expression and clinicopathology in HGSC patients. The tumor-related regulatory mechanisms of TRPS1 was explored through in vivo and vitro experiments. The results showed that TRPS1 was highly expressed in HGSC compared to normal tissues. It was also linked to the cell proliferation index Ki67 and poor prognosis. In vivo experiments showed that knockdown of TRPS1 could inhibit tumor growth. In vitro experiments, knockdown of TRPS1 inhibited the proliferation of ovarian cancer cells. TRPS1 exerted its regulatory role as a transcription factor, binding to the PSAT1 promoter and promoting the expression of PSAT1 gene. Meanwhile, PSAT1 was positively correlated with CCND1 expression. These results suggest that TRPS1 affects HGSC proliferation and cell cycle by regulating PSAT1 and thus CCND1 expression.
2023-12-11 | GSE249935 | GEO