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Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer.

ABSTRACT: Objective:To screen some RNAs that correlated with colorectal cancer (CRC). Methods:Differentially expressed miRNAs, lncRNAs, and mRNAs between cancer tissues and normal tissues in CRC were identified using data from the Gene Expression Omnibus (GEO) database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interactions (PPIs) were performed to do the functional enrichment analysis. And a lncRNA-miRNA-mRNA network was constructed which correlated with CRC. RNAs in this network were subjected to analyze the relationship with the patient prognosis. Results:A total of 688, 241, and 103 differentially expressed genes (diff-mRNA), diff-lncRNA, and diff-miRNA were obtained between cancer tissues and normal tissues. A total of 315 edges were obtained in the ceRNA network. lncRNA RP11-108K3.2 and mRNA ONECUT2 correlated with prognosis. Conclusion:The identified RNAs and constructed ceRNA network could provide great sources for the researches of therapy of the CRC. And the lncRNA RP11-108K3.2 and mRNA ONECUT2 may serve as a novel prognostic predictor of CRC.

SUBMITTER: Hui Z

PROVIDER: S-EPMC7191371 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer.

Hui Zhao Z Zhanwei Wang W Xi Yang Y Jin Liu L Jing Zhuang Z Shuwen Han H

Disease markers 20200421

<h4>Objective</h4>To screen some RNAs that correlated with colorectal cancer (CRC).<h4>Methods</h4>Differentially expressed miRNAs, lncRNAs, and mRNAs between cancer tissues and normal tissues in CRC were identified using data from the Gene Expression Omnibus (GEO) database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interactions (PPIs) were performed to do the functional enrichment analysis. And a lncRNA-miRNA-mRNA network was constructed which correlated wit ...[more]

PMID: 32377269

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Project description:ObjectiveSince circRNA can be utilized as a potential diagnostic marker for cancer, to explore the regulatory mechanism of colorectal cancer (CRC) using bioinformatics, the public database of circRNA was mined.MethodsCRC differentially expressed miRNAs were screened in the Cancer Genome Atlas (TCGA) database, CRC differentially expressed circRNAs were searched in the Gene Expression Omnibus (GEO) database, the two databases were combined to identify CRC differentially expressed mRNAs, and a circRNA-miRNA‒mRNA regulatory network was constructed by combining a plurality of target prediction databases to identify key genes. The upstream circRNA and regulatory axis of the key genes were identified for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis to explore the biological functions of circRNA in CRC using the regulatory axis.ResultsAfter the screening of the GSE21815 dataset, a total of 22 differentially expressed circRNAs were obtained, with 12 upregulated and 10 downregulated genes. Similarly, the GSE126094 dataset yielded 104 differentially expressed circRNAs, comprising 56 upregulated and 48 downregulated genes. Among the differentially expressed circRNAs, five were identified, with VDAC3 and SETD2 showing downregulated expression, while RAD23B, RPPH1, and MYBL2 exhibited upregulated expression. Following the selection process, five DEcircRNAs, eight target miRNAs, and 105 target DEmRNAs were identified. The protein-protein interaction (PPI) network revealed close relationships among the mRNAs, with E2F2, E2F3, CCND1, TNRC6A, and KAT2B identified as key genes. Notably, CCND1 emerged as a critical gene in the PPI network. Through the upregulation of has-circ-0087862, which binds to miR-892b, the translation inhibition of CCND1 by miR-892b was attenuated, leading to enhanced CCND1 expression. Functional enrichment analysis indicated that CCND1 was involved in protein binding and positive regulation of cellular processes, among other functions.ConclusionThe differentially expressed genes (DEGs) in CRC markedly affected the survival time of patients. CircRNAs could be utilized as diagnostic markers of CRC, and the key genes in CRC could be screened out by bioinformatics, which would be helpful to understand the drug targets for the treatment of human immunodeficiency virus (HIV)-related CRC patients.

Project description:BackgroundTo date, vascular dementia (VaD) lacks effective treatment in clinical practice. There is also growing evidence that VaD may be closely related to the immune response. The development of high-throughput technology, and the recently discovered group of new mediators called competitive endogenous RNAs (ceRNA), provides a unique opportunity to study the immunomodulation of VaD.MethodsIn this study, we used gene expression profiles in the Gene Expression Omnibus (GEO) database to obtain immune-related gene coexpression modules through a weighted gene coexpression network analysis (WGCNA) and gene enrichment analysis. We extracted and merged long non-coding RNA (lncRNA) and microRNA (miRNA) expressions from the GEO database and mapped them with related databases. Subsequently, we used Cytoscape to construct a lncRNA-miRNA-mRNA network, and then we performed an enrichment analysis on the mRNAs in the network to determine their regulatory function. Subsequently, we used an ImmuCellAI immune infiltration analysis and constructed a ceRNA sub-network of related immune cells. Finally, we conducted a gene set enrichment analysis (GSEA) to determine the potential regulatory pathways of the key factors.ResultsAs a result, we identified the blue module as the key module of immunity and constructed the related CeRNA network. Immune infiltration analysis showed that natural killer T (NKT) cells may be the key immune cells of VaD. Using a Pearson correlation analysis, we identified that B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1 may be the key factors of VaD. Our subsequent GSEA analysis showed that lncRNA NEAT1 may be regulated by NK cells and toll-like receptors.ConclusionsOur research provides new therapeutic targets for vascular dementia from the immunological perspective for the first time, including B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1, and our research hopes to provide new treatment options for VaD.

Project description:BackgroundMilk fat is one of the main reference elements for evaluating milk quality and is a primary objective trait in dairy cattle breeding. In recent years, circular RNAs (circRNAs) have been found to play crucial roles in many biological processes. However, the function and expression profiles of circRNAs in milk fat synthesis in cows are not completely understood. We performed RNA sequencing to analyze the genome-wide expression of circRNA transcripts in bovine mammary epithelial cells (BMECs) from cows with extreme differences in milk fat percentage. We identified candidate differential circRNAs associated with milk fat metabolism using functional enrichment analysis and constructed a lipid metabolism-related competing endogenous RNA (ceRNA) interactive regulatory network.ResultsA total of 290 circRNAs were significantly differentially expressed (DE-circRNAs) in high milk fat percentage (HMF) cows compared to that in low milk fat percentage (LMF) cows. Of the 290 circRNAs, 142 were significantly upregulated and 148 were significantly downregulated. Enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) identified four DE-circRNAs (circ_0001122, circ_0007367, circ_0018269, and circ_0015179) that potentially regulate milk fat metabolism. Among them, circ_0001122, circ_0007367, and circ_0015179 had relatively high expression levels in cow mammary gland tissue compared to other tissues (heart, liver, kidney, uterus, ovaries, and small intestine) of cows. The regulatory networks circ_0001122:miR-12043:LIPG, circ_0007367:miR-331-3p:CIDEA/PML, and circ_0018269:miR-11989:RORC/HPX are potential networks to explore the mechanism of milk fat regulation.ConclusionsThese results reveal the possible role of circRNAs in milk fat metabolism in dairy cows. Several important circRNAs and ceRNAs affecting milk fat synthesis were identified, providing insights into the complex biology of milk fat synthesis as well as a novel theoretical perspective for future research on lactation, milk quality, and breed improvement in dairy cows.

Dataset Information

Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer.

Publications

Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer.

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