Cyclin B1 expression as an independent prognostic factor for lung adenocarcinoma and its potential pathways
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE207450 | GEO | 2022/07/08
REPOSITORIES: GEO
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Project description:When cells enter mitosis, the anaphase-promoting complex/cyclosome (APC/C) is activated by phosphorylation and binding of Cdc20. The RXXL destruction box (D-box) of cyclin B1 only binds Cdc20 after release of the spindle checkpoint in metaphase, initiating cyclin B1 ubiquitination upon chromosome bi-orientation. However, we found that cyclin B1, through Cdk1 and Cks, is targeted to the phosphorylated APC/C(Cdc20) at the start of prometaphase, when the spindle checkpoint is still active. Here, we show that MASTL is essential for cyclin B1 recruitment to the mitotic APC/C and that this occurs entirely independently of Cdc20. Importantly, MASTL-directed binding of cyclin B1 to spindle checkpoint-inhibited APC/C(Cdc20) critically supports efficient cyclin B1 destruction after checkpoint release. A high incidence of anaphase bridges observed in response to MASTL RNAi may result from cyclin B1 remaining after securin destruction, which is insufficient to keep MASTL-depleted cells in mitosis but delays the activation of separase.
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Project description:Microtubule inhibitors are widely used in cancer chemotherapy. These drugs characteristically induce mitotic arrest and cell death but the mechanisms linking the two are not firmly established. One of the problems is that cancer cells vary widely in their sensitivity to these agents, and thus comparison of data from different systems is difficult. To alleviate this problem we sought to molecularly induce mitotic death and study its mechanisms, by expressing non-degradable cyclin B (R42A) in HeLa cells. However, this approach failed to induce significant mitotic arrest, Cdk1 activation, or phosphorylation of anti-apoptotic Bcl-2 proteins, all characteristics of cells treated with microtubule inhibitors. Furthermore, cyclin B1-R42A induced rapid cell death, and when expressed in synchronized cells, cell death occurred in G1 phase. Decreasing the plasmid concentration reduced transfection efficiency but restored mitotic arrest and eliminated non-specific death. These results show that inappropriate overexpression of cyclin B1 causes non-specific cell death and suggest caution in its use for the study of mitotic events.
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Project description:Cyclin B1 expression as an independent prognostic factor for lung adenocarcinoma and its potential pathways
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Project description:To determined ZBTB11 and SET regulates genes in NCI-H1299, we esteblished NCI-H1299 cell lines in which ZBTB11 and SET has been knocked down by si-RNA. We then conducted differential expressed genes analysis using data generated form RNA-seq of H1299 cell lines at the condition of two genes knocked down.
2023-12-21 | GSE206957 | GEO
Project description:Cyclin B1 is a key mitotic cyclin in the G2-M phase transition of the cell cycle and is overexpressed in various malignant tumors. Numerous studies have reported contradictory evidences of the correlation between cyclin B1 expression and prognosis in human solid tumors. To address this discrepancy, we conducted a meta-analysis with 17 published studies searched from PubMed and Medline. Cyclin B1 overexpression was significantly associated with poor 3-year overall survival (OS) (OR = 2.05, 95% CI = 1.20 to 3.50, P = 0.009) and 5-year OS (OR = 2.11, 95% CI = 1.33 to 3.36, P = 0.002) of solid tumors. Subgroup analysis revealed that elevated cyclin B1 expression was associated with worse prognosis of lung cancer and esophageal cancer but better prognosis of colorectal cancer. In summary, overexpression of cyclin B1 is correlated with poor survival in most solid tumors, which suggests that the expression status of cyclin B1 is a significant prognostic parameter in solid tumors.
| S-EPMC5356794 | biostudies-other
Project description:Aims: The biological functions of cyclin B1 (CCNB1) in colon adenocarcinoma (COAD) will be explored in this study. Furthermore, the therapeutic effects and potential molecular mechanisms of ursolic acid (UA) in COAD cells will also be investigated in vitro. Methods: COAD data were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Differentially expressed genes (DEGs) were determined with differential analysis. The biological functions of CCNB1 were analyzed through the GeneCards, the Search Tool for the Retrieval of Interacting Genes (STRING), and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) databases. Therapeutic effects of UA on COAD cell lines HCT-116 and SW-480 were analyzed by CCK-8 and high-content screening (HCS) imaging assay. Flow cytometry was utilized to detect cell cycle changes of SW-480 and HCT-116 cells. Levels of mRNA and expression proteins of HCT-116, SW-480, and normal colon epithelial cells NCM-460 were determined by qRT-PCR and western blot. Results: CCNB1 was highly expressed and acted as an oncogene in COAD patients. CCNB1 and its interacting genes were significantly enriched in the cell cycle pathway. UA effectively inhibited the proliferation and injured COAD cells. In addition, UA arrested cell cycle of COAD cells in S phase. With regard to the molecular mechanisms of UA, we demonstrated that UA can significantly downregulate CCNB1 and its interacting genes and proteins, including CDK1, CDC20, CCND1, and CCNA2, which contributed to cell cycle blocking and COAD treatment. Conclusion: Results from this study revealed that UA possesses therapeutic effects on COAD. The anti-COAD activities of UA are tightly related to suppression of CCNB1 and its interacting targets, which is crucial in abnormal cell cycle process.
| S-EPMC7898669 | biostudies-literature
Project description:PTK7 was identified from a meta-analysis of 1905 non-small-cell lung cancer (NSCLC) samples across 12 datasets to be one of seven genes commonly up-regulated in lung adenocarcinoma (ADC). Using ADC cell lines NCI-H1299 and NCI-H2009, disruption of PTK7 resulted in decreased cell viability and induction of apoptosis. A xenotransplantation model of the cell lines with PTK7 knock-down also resulted in decreased tumor burden. We assayed gene expression in these cell lines after PTK7 knock-down by shRNA to uncover deregulated pathways and genes. 8 samples were analyzed. In each cell line, we knocked down PTK7 with 2 independent hairpins, and 2 control hairpins targeting luciferase and GFP. Thus, NCI-H1299 has 2 samples of PTK7 knock-down, and 2 samples of control knock down. NCI-H2009 has similar samples.
2014-01-01 | E-GEOD-50138 | biostudies-arrayexpress
Project description:BackgroundGlucosamine-Phosphate N-Acetyltransferase 1 (GNPNAT1) is a critical enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine. It has many important functions, such as protein binding, monosaccharide binding, and embryonic development and growth. However, the role of GNPNAT1 in lung adenocarcinoma (LUAD) remains unclear.MethodsIn this study, we explored the expression pattern and prognostic value of GNPNAT1 in LUAD across TCGA and GEO databases and assessed its independent prognostic value via Cox analysis. LinkedOmics and GEPIA2 were applied to investigate coexpression and functional networks associated with GNPNAT1. The TIMER web tool was deployed to assess the correlation between GNPNAT1 and the main six types of tumor-infiltrating immune cells. Besides, the correlations between GNPNAT1 and the LUAD common genetic mutations, TMB, and immune signatures were examined.ResultsGNPNAT1 was validated upregulated in tumor tissues in TCGA-LUAD and GEO cohorts. Moreover, in both TCGA and GEO cohorts, high GNPNAT1 expression was found to be associated with poor overall survival. Cox analysis showed that high GNPNAT1 expression was an independent risk factor for LUAD. Functional network analysis suggested that GNPNAT1 regulates cell cycle, ribosome, proteasome, RNA transport, and spliceosome signaling through pathways involving multiple cancer-related kinases and E2F family. In addition, GNPNAT1 correlated with infiltrating levels of B cells, CD4+ T cells, and dendritic cells. B cells and dendritic cells could predict the outcome of LUAD, and B cells and CD4+ T cells were significant independent risk factors. The TMB and mutations of KRAS, EGFR, STK11, and TP53 were correlated with GNPNAT1. At last, the correlation analysis showed GNPNAT1 correlated with most of the immune signatures we performed.ConclusionOur findings showed that GNPNAT1 was correlated to the prognosis and immune infiltration of LUAD. In particular, the tight relationship between GNPNAT1 and B cell marker genes may be the epicenter of the immune response and one of the key factors affecting the prognosis. Our findings laid the foundation for further research on the immunomodulatory role of GNPNAT1 in LUAD.
| S-EPMC7648248 | biostudies-literature
Project description:In our study, we found that profilin 1 (PFN1) promoted non-small cell lung cancer (NSCLC) metastasis.For further investigate the mechanisms of PFN1's roles in NSCLC metastasis, we constructed PFN1 overxpression H1299 cell lines(H1299 PFN1 OE cells). And we sent samples of H1299 PFN1 OE cells and EV cells for TMT based quantative proteome profiling.
2022-04-14 | PXD033148 | Pride
Project description:ObjectivesThe present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters.MethodsThe ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein-protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments.ResultsThe stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity.ConclusionsThe ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.
| S-EPMC8168034 | biostudies-literature