Construction of an oesophageal cancer-specific ceRNA network based on miRNA, lncRNA, and mRNA expression data.
Ontology highlight
ABSTRACT:
SUBMITTER: Xue WH
PROVIDER: S-EPMC5757122 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
Construction of an oesophageal cancer-specific ceRNA network based on miRNA, lncRNA, and mRNA expression data.
Xue Wen-Hua WH Fan Zhi-Rui ZR Li Li-Feng LF Lu Jing-Li JL Ma Bing-Jun BJ Kan Quan-Cheng QC Zhao Jie J
World journal of gastroenterology 20180101 1
<h4>Aim</h4>To explore the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and mRNAs in oesophageal squamous cell carcinoma (ESCC) in order to construct an oesophageal cancer-specific competing endogenous RNA (ceRNA) network.<h4>Methods</h4>In this work, the expression data of miRNAs, lncRNAs, and mRNAs in ESCC were obtained. An oesophageal cancer-specific ceRNA network was then constructed and investigated.<h4>Results</h4>CeRNAs have the ability to reduce the targetin ...[more]
Similar Datasets
Project description:Long non-coding RNAs (lncRNAs) are ncRNA transcripts >200 nucleotides that are important genetic regulators. LncRNAs can directly regulate mRNA through a lncRNA-mRNA regulatory mode and can also regulate mRNA through competitive binding to micro (mi)RNA, which is generally known as the competitive endogenous RNA (ceRNA) network. The present study evaluated the functional roles and regulatory networks of lncRNAs in chronic glomerulonephritis (CGN). The proliferative ability of mouse glomerular mesangial cells (GMCs) induced by different concentrations of lipopolysaccharide (LPS) was assessed using the Cell Counting Kit-8 assay, and RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs in LPS-induced GMCs. Based on the sequencing results, six lncRNAs were selected for validation using reverse transcription-quantitative PCR (RT-qPCR). Furthermore, the lncRNA-mRNA regulatory network and the lncRNA-miRNA-mRNA ceRNA network were constructed to assess the role and mechanism of CGN-related lncRNAs. To elucidate the biological functions of lncRNAs, Gene Ontology (GO) biological process term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on all mRNAs involved in the lncRNA-mRNA regulatory network and in the ceRNA network. A total of 1,532 differentially expressed lncRNAs, including 594 upregulated lncRNAs and 938 downregulated lncRNAs, were identified using RNA-seq. The results of RT-qPCR validation were consistent with RNA-seq results. An lncRNA-mRNA regulatory network, including 236 lncRNAs and 556 mRNAs, and a ceRNA network, including 6 lncRNAs, 18 miRNAs and 419 mRNAs, were successfully constructed. The GO biological process term enrichment and KEGG pathway enrichment analyses demonstrated that those lncRNAs were often related to inflammatory response and substance metabolism. The present study identified key CGN-related lncRNAs in LPS-induced GMCs, and further demonstrated a global view of the lncRNA-mRNA regulatory network and ceRNA network involved in CGN. These results offered novel insights into the roles of lncRNAs in the pathogenesis of CGN and identified potential diagnostic biomarkers.
| S-EPMC10375445 | biostudies-literature
Project description:It has been proved and widely acknowledged that messenger RNAs can talk to each other by competing for a limited pool of miRNAs. The competing endogenous RNAs are called as ceRNAs. Although some researchers have recently used ceRNAs to do biological function annotations, few of them have investigated the ceRNA network on specific disease systematically. In this work, using both miRNA expression data and mRNA expression data of breast cancer patient as well as the miRNA target relations, the authors proposed a computational method to construct a breast-cancer-specific ceRNA network by checking whether the shared miRNA sponges between the gene pairs are significant. The ceRNA network is shown to be scale-free, thus the topological characters such as hub nodes and communities may provide important clues for the biological mechanism. Through investigation on the communities (the dense clusters) in the network, it was found that they are related to cancer hallmarks. In addition, through function annotation of the hub genes in the network, it was found that they are related to breast cancer. Moreover, classifiers based on the discriminative hubs can significantly distinguish breast cancer patients' risks of distant metastasis in all the three independent data sets.
| S-EPMC8687191 | biostudies-literature
Project description:ObjectiveTo identify differentially expressed lncRNA, miRNA, and mRNA during the pathogenesis of gout, explore the ceRNA network regulatory mechanism of gout, and seek potential therapeutic targets.MethodFirst, gout-related chips were retrieved by GEO database. Then, the analysis of differentially expressed lncRNAs and mRNAs was conducted by R language and other software. Besides, miRNA and its regulated mRNA were predicted based on public databases, the intersection of differentially expressed mRNA and predicated mRNA was taken, and the lncRNA-miRNA-mRNA regulatory relationships were obtained to construct the ceRNA regulatory network. Subsequently, hub genes were screened by the STRING database and Cytoscape software. Then the DAVID database was used to illustrate the gene functions and related pathways of hub genes and to mine key ceRNA networks.ResultsThree hundred and eighty-eight lncRNAs and 758 mRNAs were identified with significant differential expression in gout patient, which regulates hub genes in the ceRNA network, such as JUN, FOS, PTGS2, NR4A2, and TNFAIP3. In the ceRNA network, lncRNA competes with mRNA for miRNA, thus affecting the IL-17 signaling pathway, TNF signaling pathway, Oxytocin signaling pathway, and NF-κB signaling pathway through regulating the cell's response to chemical stress. The research indicates that five miRNAs (miR-429, miR-137, miR-139-5p, miR-217, miR-23b-3p) and five lncRNAs (SNHG1, FAM182A, SPAG5-AS1, HNF1A-AS1, UCA1) play an important role in the formation and development of gout.ConclusionThe interaction in the ceRNA network can affect the formation and development of gout by regulating the body's inflammatory response as well as proliferation, differentiation, and apoptosis of chondrocytes and osteoclasts. The identification of potential therapeutic targets and signaling pathways through ceRNA network can provide a reference for further research on the pathogenesis of gout.
| S-EPMC9169187 | biostudies-literature
Project description:Accumulating evidence has indicated that noncoding RNAs are involved in intervertebral disc degeneration (IDD); however, the competing endogenous RNA (ceRNA)‑mediated regulatory mechanisms in IDD remain rarely reported. The present study aimed to comprehensively investigate the alterations in expression levels of circular RNA (circRNA), long noncoding RNA (lncRNA), microRNA (miRNA/miR) and mRNA in the nucleus pulposus (NP) of patients with IDD. In addition, crucial lncRNA/circRNA‑miRNA‑mRNA ceRNA interaction axes were screened using the GSE67567 microarray dataset obtained from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs) or genes (DEGs) between IDD and normal controls were identified using the Linear Models for Microarray data method. A protein‑protein interaction (PPI) network was constructed for DEGs based on protein databases, followed by module analysis. The ceRNA network was constructed based on the interaction between miRNAs and mRNAs, and lncRNAs/circRNAs and miRNAs. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery database. The present study identified 636 DECs, 115 DELs, 84 DEMs and 1,040 DEGs between patients with IDD and control individuals. PPI network analysis demonstrated that Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS), mitogen‑activated protein kinase 1 (MAPK1), hypoxia inducible factor 1 subunit α (HIF1A) and transforming growth factor β1 (TGFB1) were hub genes and enriched in modules. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1)/hsa_circRNA_102348‑hsa‑miR‑185‑5p‑TGFB1/FOS, MALAT1‑hsa‑miR‑155‑5p‑HIF1A, hsa_circRNA_102399‑hsa‑miR‑302a‑3p‑HIF1A, MALAT1‑hsa‑miR‑519d‑3p‑MAPK1 and hsa_circRNA_100086‑hsa‑miR‑509‑3p‑MAPK1 ceRNA axes were obtained by constructing the ceRNA networks. In conclusion, these identified ceRNA interaction axes may be crucial targets for the treatment of IDD.
| S-EPMC6755180 | biostudies-literature
Project description:Liver hepatocellular carcinoma (LIHC) is one of the major causes of cancer-related death worldwide with increasing incidences, however there are very few studies about the underlying mechanisms and pathways in the development of LIHC. We obtained LIHC samples from The Cancer Genome Atlas (TCGA) to screen differentially expressed mRNAs, lncRNAs, miRNAs and driver mutations. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses and protein-protein interaction (PPI) network were performed. Moreover, we constructed a competing endogenous lncRNAs-miRNAs-mRNAs network. Finally, cox proportional hazards regression analysis was used to identify important prognostic differentially expressed genes. Total of 1284 mRNAs, 123 lncRNAs, 47 miRNAs were identified within different tissues of LIHC patients. GO analysis indicated that upregulated and downregulated differentially expressed mRNAs (DEmRNAs) were mainly associated with cell division, DNA replication, mitotic sister chromatid segregation and complement activation respectively. Meanwhile, KEGG terms revealed that upregulated and downregulated DEmRNAs were primarily involved in DNA replication, Metabolic pathways, cell cycle and Metabolic pathways, chemical carcinogenesis, retinol metabolism pathway respectively. Among the DERNAs, 542 lncRNAs-miRNAs-mRNAs pairs were predicted to construct a ceRNA regulatory network including 35 DElncRNAs, 26 DEmiRNAs and 112 DEmRNAs. In the Kaplan-Meier analysis, total of 43 mRNAs, 14 lncRNAs and 3 miRNAs were screened out to be significantly correlated with overall survival of LIHC. The mutation signatures were analyzed and its correlation with immune infiltrates were evaluated using the TIMER in LIHC. Among the mutation genes, TTN mutation is often associated with poor immune infiltration and a worse prognosis in LIHC. This work conducted a novel lncRNAs-miRNAs-mRNAs network and mutation signatures for finding potential molecular mechanisms underlying the development of LIHC. The biomarkers also can be used for predicting prognosis of LIHC.
| S-EPMC8051809 | biostudies-literature
Project description:Understanding the molecular pattern of fertility is considered as an important step in breeding of different species, and despite the high importance of the fertility, little success has been achieved in dissecting the interactome basis of sheep fertility. However, the complex mechanisms associated with prolificacy in sheep have not been fully understood. Therefore, this study aimed to use competitive endogenous RNA (ceRNA) networks to evaluate this trait to better understand the molecular mechanisms responsible for fertility. A competitive endogenous RNA (ceRNA) network of the corpus luteum was constructed between Romanov and Baluchi sheep breeds with either good or poor genetic merit for prolificacy using whole-transcriptome analysis. First, the main list of lncRNAs, miRNAs, and mRNA related to the corpus luteum that alter with the breed were extracted, then miRNA-mRNA and lncRNA-mRNA interactions were predicted, and the ceRNA network was constructed by integrating these interactions with the other gene regulatory networks and the protein-protein interaction (PPI). A total of 264 mRNAs, 14 lncRNAs, and 34 miRNAs were identified by combining the GO and KEGG enrichment analyses. In total, 44, 7, 7, and 6 mRNAs, lncRNAs, miRNAs, and crucial modules, respectively, were disclosed through clustering for the corpus luteum ceRNA network. All these RNAs involved in biological processes, namely proteolysis, actin cytoskeleton organization, immune system process, cell adhesion, cell differentiation, and lipid metabolic process, have an overexpression pattern (Padj < 0.01). This study increases our understanding of the contribution of different breed transcriptomes to phenotypic fertility differences and constructed a ceRNA network in sheep (Ovis aries) to provide insights into further research on the molecular mechanism and identify new biomarkers for genetic improvement.
| S-EPMC9332185 | biostudies-literature
Project description:BackgroundMany studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in aortic dissection (AD) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in aortic dissection on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network.MethodsThis study collected the lncRNAs (GSE52093), mRNAs (GSE52093) and miRNAs (GSE92427) expression data within human tissue samples with aortic dissection group and normal group based on Gene Expression Omnibus (GEO) database.ResultsThis study identified three differentially expressed lncRNAs (DELs), 19 differentially expressed miRNAs (DEmiRs) and 1046 differentially expressed mRNAs (DEGs) identified regarding aortic dissection. Furthermore, we constructed a lncRNA-miRNA-mRNA network through three lncRNAs (including two with up-regulation and one with down-regulation), five miRNAs (five with up-regulation), as well as 211 mRNAs (including 103 with up-regulation and 108 with down-regulation). Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, four critical genes were found (E2F2, IGF1R, BDNF and PPP2R1B). In addition, E2F2 level was possibly modulated via lncRNA FAM87A-hsa-miR-31-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. The expression of IGF1R may be regulated by lncRNA FAM87A-hsa-miR-16-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p.ConclusionIn conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating AD. Our results shed more lights on the possible pathogenic mechanism in AD using a lncRNA-associated ceRNA network.
| S-EPMC8495997 | biostudies-literature
Project description:BackgroundThis study aims to explore the molecular mechanism of negative pressure wound therapy (NPWT) at the transcriptome level through whole transcriptome sequencing and biometric analysis.MethodsA rat skin defect model was constructed and randomly divided into a NPWT group and a gauze group. The tissue in the center of the wound was used for whole transcriptome sequencing, and differentially expressed messenger RNAs (DEmRNAs), long noncoding RNAs (DElncRNAs), and microRNAs (DEmiRNAs) were identified between the two groups. Quantitative real time-polymerase chain reaction (qRT-PCR) analysis was used to verify the sequencing results. Functional enrichment analysis, pathway analysis, and protein-protein interaction (PPI) network analysis of DEmRNAs were conducted. Through bioinformatics analysis, a lncRNA-associated competing endogenous RNA (ceRNA) network was identified and constructed.ResultsWe detected 896 DEmRNAs, 1,471 DElncRNAs, and 20 DEmiRNAs between the two groups. qRT-PCR verified the sequencing results. Functional analysis showed that DEmRNAs were mainly enriched in immune system processes and the Notch signaling pathway. Protein tyrosine phosphatase receptor type C (PTPRC) and signal transducer and activator of transcription 1 (STAT1) were the central hub nodes in the PPI analysis. The ceRNA network contained 11 mRNAs, 15 lncRNAs, and 4 miRNAs.ConclusionsWe identified several DEmRNAs, DElncRNAs, and DEmiRNAs between the NPWT treatment group and the control group. These findings may provide new insights into the pathophysiological mechanism of NPWT and wound healing.
| S-EPMC8506533 | biostudies-literature
Project description:Background: Hepatocellular carcinoma (HCC) accounts for the majority of liver cancer, with the incidence and mortality rates increasing every year. Despite the improvement of clinical management, substantial challenges remain due to its high recurrence rates and short survival period. This study aimed to identify potential diagnostic and prognostic biomarkers in HCC through bioinformatic analysis. Methods: Datasets from GEO and TCGA databases were used for the bioinformatic analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out by WebGestalt website and clusterProfiler package of R. The STRING database and Cytoscape software were used to establish the protein-protein interaction (PPI) network. The GEPIA website was used to perform expression analyses of the genes. The miRDB, miRWalk, and TargetScan were employed to predict miRNAs and the expression levels of the predicted miRNAs were explored via OncomiR database. LncRNAs were predicted in the StarBase and LncBase while circRNA prediction was performed by the circBank. ROC curve analysis and Kaplan-Meier (KM) survival analysis were performed to evaluate the diagnostic and prognostic value of the gene expression, respectively. Results: A total of 327 upregulated and 422 downregulated overlapping DEGs were identified between HCC tissues and noncancerous liver tissues. The PPI network was constructed with 89 nodes and 178 edges and eight hub genes were selected to predict upstream miRNAs and ceRNAs. A lncRNA/circRNA-miRNA-mRNA network was successfully constructed based on the ceRNA hypothesis, including five lncRNAs (DLGAP1-AS1, GAS5, LINC00665, TYMSOS, and ZFAS1), six circRNAs (hsa_circ_0003209, hsa_circ_0008128, hsa_circ_0020396, hsa_circ_0030051, hsa_circ_0034049, and hsa_circ_0082333), eight miRNAs (hsa-miR-150-5p, hsa-miR-19b-3p, hsa-miR-23b-3p, hsa-miR-26a-5p, hsa-miR-651-5p, hsa-miR-10a-5p, hsa-miR-214-5p and hsa-miR-486-5p), and five mRNAs (CDC6, GINS1, MCM4, MCM6, and MCM7). The ceRNA network can promote HCC progression via cell cycle, DNA replication, and other pathways. Clinical diagnostic and survival analyses demonstrated that the ZFAS1/hsa-miR-150-5p/GINS1 ceRNA regulatory axis had a high diagnostic and prognostic value. Conclusion: These results revealed that cell cycle and DNA replication pathway could be potential pathways to participate in HCC development. The ceRNA network is expected to provide potential biomarkers and therapeutic targets for HCC management, especially the ZFAS1/hsa-miR-150-5p/GINS1 regulatory axis.
| S-EPMC8977626 | biostudies-literature
Project description:BackgroundNumerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear.MethodsThe miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network.ResultsIn total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 - AS, FOXD2 - AS1, AC105277.1, AC099850.3, STARD4 - AS1, SLC16A1 - AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR - 654, miR - 503, miR - 450a, miR - 379, miR - 369, miR - 190a, miR - 101, and let-7c) were found to be significantly associated with overall survival (log-rank p < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT.ConclusionsIn this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.
| S-EPMC6686570 | biostudies-literature