Dataset Information

Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma.

ABSTRACT: PURPOSE:To investigate the role of SET domain containing 7 (SETD7) in hepatocellular carcinoma (HCC) and determine whether SETD7 can be used as a predictor of overall survival in HCC patients. METHODS:mRNAs and proteins of SETD7 and related genes in HCC tumor samples and paired adjacent non-tumorous liver tissues (ANLTs) (n = 20) or culture cells were determined by quantitative real-time PCR and Western blot. Cell proliferation and apoptosis with SETD7 knockdown SMMC-7721 cells or SETD7 overexpressed HepG2 cells were analyzed by CCK8 assay or flow cytometry. Gene expression alterations in SETD7 knockdown of SMMC-7721 cells were determined by digital gene expression (DGE) profiling. Defined data on patients (n = 225) with HCC were retrieved for the further study. Tissue microarrays (TMAs) were performed using paraffin tissues with tumor and ANLTs. SETD7 and related proteins were determined by TMAs immunohistochemistry. Statistical analyses were conducted to associate SETD7 expression with tumor features and patient outcomes, as well as related proteins expression. RESULTS:SETD7 expression was significantly higher in HCC tumor tissues than in ANLTs. SETD7 overexpression in vitro can promote HepG2 cell proliferation, whereas SETD7 knockdown can inhibit SMMC-7721 cell proliferation by regulating the cell cycle. SETD7 expression was significantly correlated with five genes expression. Increased SETD7 is associated with metastasis, recurrence, large tumor size, and poor tumor differentiation, and indicates poor prognosis in HCC patients. CONCLUSIONS:SETD7 plays a critical role in HCC, and its immunohistochemistry signature provides potential clinical significance for personalized prediction of HCC prognosis.

SUBMITTER: Chen Y

PROVIDER: S-EPMC4868314 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma.

Chen Yuanyuan Y Yang Shengsheng S Hu Jiewei J Yu Chaoqin C He Miaoxia M Cai Zailong Z

PloS one 20160516 5

<h4>Purpose</h4>To investigate the role of SET domain containing 7 (SETD7) in hepatocellular carcinoma (HCC) and determine whether SETD7 can be used as a predictor of overall survival in HCC patients.<h4>Methods</h4>mRNAs and proteins of SETD7 and related genes in HCC tumor samples and paired adjacent non-tumorous liver tissues (ANLTs) (n = 20) or culture cells were determined by quantitative real-time PCR and Western blot. Cell proliferation and apoptosis with SETD7 knockdown SMMC-7721 cells or ...[more]

PMID: 27183310

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Project description:Objective:Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients. Methods:The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan-Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways. Results:The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype. Conclusion:Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.

Project description:BackgroundDysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear.MethodsGene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets.ResultsWe showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC.ConclusionsOur study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.

Project description:BackgroundLung adenocarcinoma (LUAD) is one of the most common types of cancer in the respiratory system, with a high mortality and recurrence rate. The role of disc large-associated protein 5 (DLGAP5) in LUAD progression and tumor microenvironment (TME) remains unclear. This study is aimed at revealing the functional role of DLGAP5 in LUAD based on bioinformatics analysis and experimental validation.MethodsDifferential expression analysis, protein-protein interaction (PPI) network, and Cox regression analysis were applied to screen potential prognostic biomarkers. The mRNA and protein levels of DLGAP5 were analyzed using The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA) databases. The CCK-8 and colony formation assays were performed to assess the effect of DLGAP5 on cell proliferation. RNA sequencing (RNA-seq) and enrichment analyses were utilized to explore the biological functions of DLGAP5. Furthermore, flow cytometry was used to explore the role of DLGAP5 on the cell cycle. The ssGSEA algorithm in the R package "GSVA" was applied to quantify immune infiltrating cells, and the tumor immune dysfunction and exclusion (TIDE) algorithm was used to predict the efficacy of immunotherapy. Moreover, analyses using the cBioPortal and MethSurv databases were performed to evaluate the mutation and methylation of DLGAP5, respectively. Finally, the prognostic value of DLGAP5 was estimated using the TCGA and the Gene Expression Omnibus (GEO) databases. The nomogram model was constructed using the TCGA-LUAD cohort and evaluated by adopting calibration curves, time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).ResultsDLGAP5 mRNA and protein abundance were significantly elevated in LUAD, and knockdown of DLGAP5 remarkably suppressed lung cancer cell proliferation through induction of cell cycle G1 arrest. In addition, DLGAP5 expression was positively correlated with Th2 cells and negatively correlated with B cells, T follicular helper cells, and mast cells. LUAD patients with high DLGAP5 expression may be resistant to immunotherapy. Hypermethylation levels of the cg23678254 site of DLGAP5 or its enhanced expression were unfavorable for the survival of LUAD patients. Meanwhile, DLGAP5 expression was associated with TNM stages, tumor status, and therapy outcome. Notably, the prognostic model constructed based on DLGAP5 expression exhibited great predictive capability, which was promising for clinical applications.ConclusionDLGAP5 promotes lung cancer cell proliferation through regulation of the cell cycle and is associated with multiple immune infiltrating cells. Furthermore, DLGAP5 predicts poor prognosis and response to immunotherapy in lung adenocarcinoma.

Dataset Information

Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma.

Publications

Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma.

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