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Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer.

ABSTRACT: Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA-related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA-miRNA-mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer-specific differentially expressed lncRNAs, miRNAs, and mRNAs were screened for constructing a ceRNA network using bioinformatic tools. The enrichment analysis of the biological processes in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathways was performed on the ceRNA-related DEmRNAs. According to the modularization of protein-protein interaction (PPI) network, we extracted a ceRNA subnetwork and analyzed the correlation between the expression of the lncRNAs involved and specific clinical features of patients. Next, the expression of highly up-regulated in liver cancer (HULC) and RP11-314B1.2 showed significant changes in several pathological processes involved in gastric cancer, and nine lncRNAs were found to be correlated with the overall survival of patients with gastric cancer. Through the univariate and multivariate Cox regression analyses, two lncRNAs (LINC00106 and RP11-999E24.3) were identified and utilized to establish a risk score model for assessing the prognosis of patients. The analysis results were also partially verified using quantitative real-time PCR. The findings from this study indicate that HULC, RP11-314B1.2, LINC00106, and RP11-999E24.3 could be considered as potential therapeutic targets or prognostic biomarkers in gastric cancer, and provide a new perspective for cancer pathogenesis research.

SUBMITTER: Qi M

PROVIDER: S-EPMC7050084 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer.

Qi Mingran M Yu Bingxin B Yu Huiyuan H Li Fan F

Cancer medicine 20200110 5

Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA-related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA-miRNA-mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer-specific differentially expressed lnc ...[more]

PMID: 31923354

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Project description:BackgroundLong noncoding RNAs (lncRNAs) play important roles in competing endogenous RNA (ceRNA) networks involved in the development and progression of various cancers, including muscle-invasive bladder cancer (MIBC).PurposeThis study aims to construct the lncRNA-associated ceRNA network and identify lncRNA signatures correlated with the clinical features of MIBC tissue samples from The Cancer Genome Atlas (TGCA) database.MethodsThe differential expression profiles of MIBC associated lncRNAs, miRNAs and mRNAs were obtained from TCGA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the principal functions of significantly dysregulated mRNAs. The dysregulated lncRNA-associated ceRNA network of MIBC was constructed based on the bioinformatics data, and the correlations between lncRNA expression and clinical features were analyzed using a weighted gene coexpression network analysis (WGCNA). Six cancer specific lncRNAs from the ceRNA network were randomly selected to detect their expression in 32 paired MIBC tissue samples and 5 bladder cancer cell lines using quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe ceRNA network was constructed with 30 lncRNAs, 13 miRNAs and 32 mRNAs. Seventeen lncRNAs in the ceRNA network correlated with certain clinical features, and only 1 lncRNA (MIR137HG) correlated with the overall survival (OS) of patients with MIBC (log-rank test P<0.05). GO and KEGG analyses revealed roles for the potential mRNA targets of MIR137HG in epithelial cell differentiation and the peroxisome proliferator-activated receptor (PPAR) and tumor necrosis factor (TNF) signaling pathways. The expression data from TCGA were highly consistent with the verification results of the MIBC tissue samples and bladder cancer cell lines.ConclusionThese findings improve our understanding of the regulatory mechanism of the lncRNA-miRNA-mRNA ceRNA network and reveal potential lncRNAs as prognostic biomarkers of MIBC.

Project description:BackgroundBreast cancer is a malignancy and lethal tumor in women. Metastasis of breast cancer is one of the causes of poor prognosis. Increasing evidences have suggested that the competing endogenous RNAs (ceRNAs) were associated with the metastasis of breast cancer. Nonetheless, potential roles of ceRNAs in regulating the metastasis of breast cancer remain unclear.MethodsThe RNA expression (3 levels) and follow-up data of breast cancer and noncancerous tissue samples were downloaded from the Cancer Genome Atlas (TCGA). Differentially expressed and metastasis associated RNAs were identified for functional analysis and constructing the metastasis associated ceRNA network by comprehensively bioinformatic analysis. The Kaplan-Meier (K-M) survival curve was utilized to screen the prognostic RNAs in metastasis associated ceRNA network. Moreover, we further identified the metastasis associated biomarkers with operating characteristic (ROC) curve. Ultimately, the data of Cancer Cell Line Encyclopedia (CCLE, https://portals.broadinstitute.org/ccle) website were selected to obtained the reliable metastasis associated biomarkers.Results1005 mRNAs, 22 miRNAs and 164 lncRNAs were screened as differentially expressed and metastasis associated RNAs. The results of GO function and KEGG pathway enrichment analysis showed that these RNAs are mainly associated with the metabolic processes and stress responses. Next, a metastasis associated ceRNA (including 104 mRNAs, 19 miRNAs, and 16 lncRNAs) network was established, and 12 RNAs were found to be related to the overall survival (OS) of patients. In addition, 3 RNAs (hsa-miR-105-5p, BCAR1, and PANX2) were identified to serve as reliable metastasis associated biomarkers. Eventually, the results of mechanism analysis suggested that BCAR1 might promote the metastasis of breast cancer by facilitating Rap 1 signaling pathway.ConclusionIn the present research, we identified 3 RNAs (hsa-miR-105-5p, BCAR1 and PANX2) might associated with prognosis and metastasis of breast cancer, which might be provide a new perspective for metastasis of breast cancer and contributed to the treatment of breast cancer.

Project description:BackgroundGastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction.MethodsThe lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs.ResultsDifferentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells.ConclusionsThe authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.

Project description:Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer. We downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Gene ontology and pathway enrichment analyses were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. A total of 72 DEcircRNAs, 158 DEmiRNAs, and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA-miRNA pairs and 140 miRNA-mRNA pairs, including 40 circRNAs, 30 miRNAs, and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in the PI3K-Akt signaling pathway, microRNAs in cancer, and proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA-mRNA interaction pairs had a significant negative correlation. A PPI network was established, and 21 hub genes were determined from the network. This study provides an effective bioinformatics basis for further understanding of the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis.

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Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer.

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Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer.

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