Dataset Information

Construction of lncRNA-miRNA-mRNA networks reveals functional lncRNAs in abdominal aortic aneurysm.

ABSTRACT: Abdominal aortic aneurysm (AAA) is one of the most significant causes of morbidity and mortality in populations aged >65 years worldwide. However, the underlying mechanisms of AAA based on the competitive endogenous RNA (ceRNA) hypothesis have remained elusive. In the present study, differently expressed long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA networks in AAA were constructed by analyzing public datasets, including GSE7084, GSE24194 from rats and that of a previous study. A total of 1,219 mRNAs, 2,093 lncRNAs and 57 miRNAs were identified to differently express in AAA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the potential roles of differently expressed lncRNAs based on their regulating mRNAs. Based on the ceRNA hypothesis, lncRNA-miRNA-mRNA networks in AAA were, for the first time, constructed at a system-wide level. The present study identified 5 upregulated lncRNAs [nuclear paraspeckle assembly transcript 1, cyclin-dependent kinase inhibitor 2B antisense RNA 1, small Cajal body-specific RNA 10, AC005224.4 and SUMO1/sentrin/SMT3-specific peptidase 3-eukaryotic translation initiation factor 4A1] and the downregulated zinc ribbon domain containing 1 antisense RNA 1 as key lncRNAs in ceRNA networks. To the best of our knowledge, the present study was the first to screen ceRNA networks in AAA. In addition, key lncRNA-mRNA-biological processes analysis indicated that these key lncRNAs were involved in regulating signal transduction, protein amino acid phosphorylation, immune response, transcription, development and cell differentiation. The present study provides novel clues to explore the molecular mechanisms of AAA progression in terms of lncRNA implication.

SUBMITTER: Tian L

PROVIDER: S-EPMC6176170 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Construction of lncRNA-miRNA-mRNA networks reveals functional lncRNAs in abdominal aortic aneurysm.

Tian Lu L Hu Xiaofeng X He Yangyan Y Wu Ziheng Z Li Donglin D Zhang Hongkun H

Experimental and therapeutic medicine 20180904 5

Abdominal aortic aneurysm (AAA) is one of the most significant causes of morbidity and mortality in populations aged >65 years worldwide. However, the underlying mechanisms of AAA based on the competitive endogenous RNA (ceRNA) hypothesis have remained elusive. In the present study, differently expressed long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA networks in AAA were constructed by analyzing public datasets, including GSE7084, GSE24194 from rats and that of a previous study. A total of 1 ...[more]

PMID: 30344676

Similar Datasets

Project description:BackgroundAbdominal aortic aneurysm (AAA) is a progressive cardiovascular disease, which is a permanent and localized dilatation of the abdominal aorta with potentially fatal consequence of aortic rupture. Dysregulation of circRNAs is correlated with the development of various pathological events in cardiovascular diseases. However, the function of circRNAs in abdominal aortic aneurysm (AAA) is unknown and remains to be explored. This study is aimed at determining the regulatory mechanisms of circRNAs in AAAs. This study was aimed at exploring the underlying molecular mechanisms of abdominal aortic aneurysms based on the competing endogenous RNA (ceRNA) regulatory hypothesis of circRNA, miRNA, and mRNA.MethodsThe expression profiles of circRNAs (GSE144431), miRNAs (GSE62179), and mRNAs (GSE7084, GSE57691, and GSE47472) in human tissue sample from the aneurysm group and normal group were obtained from the Gene Expression Omnibus database, respectively. The circRNA-miRNA-mRNA network was constructed by using Cytoscape 3.7.2 software; then, the protein-protein interaction (PPI) network was constructed by using the STRING database, and the hub genes were identified by using the cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in AAAs.ResultsThe present study identified 40 differentially expressed circRNAs (DECs) in the GSE144431, 90 differentially expressed miRNAs (DEmiRs) in the GSE62179, and 168 differentially expressed mRNAs (DEGs) with the same direction regulation (130 downregulated and 38 upregulated) in the GSE7084, GSE57691, and GSE47472 datasets identified regarding AAAs. The miRNA response elements (MREs) of three DECs were then predicted. Four overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 17 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of 4 miRNAs with 168 DEGs. Furthermore, the circRNA-miRNA-mRNA network was constructed through 3 circRNAs, 4 miRNAs, and 17 mRNAs, and three hub genes (SOD2, CCR7, and PGRMC1) were identified. Simultaneously, functional enrichment and pathway analysis were performed within genes in the circRNA-miRNA-mRNA network. Three of them (SOD2, CCR7, and PGRMC1) were suggested to be crucial based on functional enrichment, protein-protein interaction, and ceRNA network analysis. Furthermore, the expression of SOD2 and CCR7 may be regulated by hsa_circ_0011449/hsa_circ_0081968/hsa-let-7f-5p; the expression of PGRMC1 may be regulated by hsa_circ_0011449/hsa_circ_0081968-hsa-let-7f-5p/hsa-let-7e-5p.ConclusionIn conclusion, the ceRNA interaction axis we identified may be an important target for the treatment of abdominal aortic aneurysms. This study provided further understanding of the potential pathogenesis from the perspective of the circRNA-related competitive endogenous RNA network in AAAs.

Project description:Abdominal aortic aneurysm (AAA) is a life-threatening disorder and, therefore, investigation into its underlying mechanisms in light of the competing endogenous RNAs (ceRNAs) hypothesis has gradually increased. However, there is still lacking systematic analysis on AAA-associated circular RNA (circRNA)-microRNA (miRNA/miR)-messenger RNA (mRNA) interaction networks based on bioinformatics methods. The present study attempted to identify novel molecular biomarkers for AAA by profiling circRNA-miRNA-mRNA networks using three public microarray datasets (GSE7084, GSE57691 and GSE144431). A total of 135 differentially expressed genes (DEGs) and 142 differentially expressed circRNAs were detected using the limma R package with the statistical threshold of P<0.05 and |log2fold change (FC)| >1.5. In addition, 12 circRNA-miRNA-mRNA axes were identified to construct upregulated and downregulated ceRNA networks using Cytoscape. Based on molecular complex detection algorithm, (hsa_circ_0057691/0092108/0006845/0082182)- miR-330-5p-calponin 1 (CNN1) and (hsa_circ_0061482/0011450/0008351/0004121)-miR-326-CD8a molecule (CD8A) were recognized as the center axes in ceRNA networks. Reverse transcription-quantitative PCR results verified the significant downregulation of CNN1 and upregulation of CD8A in human AAA tissues (P<0.05). In addition, four upregulated circRNA/mRNA axes, and five downregulated circRNA/mRNA axes were revealed to have possible biological functions in the pathogenesis of AAA using the Cytoscape software. Receiver operating characteristic analysis demonstrated the accuracy of these nine DEGs involved in these axes for AAA diagnosis with area under the curves >0.80. The present study revealed novel circRNA-miRNA-mRNA networks associated with AAA, especially for CNN1 and CD8A axes with the potential function of 'focal adhesion' and 'immune response', respectively. Overall, the present findings may provide evidence to explore the implicated ceRNAs in the molecular mechanisms and as novel biomarkers for AAA.

Project description:Background: Ovarian cancer (OC) is the most lethal malignancy in the female reproductive system. Growing evidences demonstrates that competing endogenous RNA (ceRNA) network play crucial roles in the occurrence and progression of tumors. Therefore, we aimed to explore and identify novel mRNA-miRNA-lncRNA ceRNA networks associated with prognosis of OC. Methods: The differentially expressed gene (DEGs) of four expression profiles datasets (GSE5438, GSE40595, GSE38666 and GSE26712) were collected from Gene Expression Omnibus (GEO) database and analyzed with NetworkAnalyst. Intersection of DEGs were further employed for Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis. Protein-protein interaction (PPI) network and hub genes of DEGs were also identified. The expression levels and survival analysis of the hub genes in OC and their upstream miRNAs and lncRNAs were performed by various bioinformatics databases. More importantly, ceRNA networks were constructed based on mRNA-miRNA-lncRNA in OC. Results: A total of 178 DEGs including 38 upregulated and 140 downregulated genes from intersected DEGs of four expression profiles were identified in OC. Functional enrichment analysis suggested that the commonly DEGs were enriched in regulating enzyme inhibitor activity, glycosaminoglycan and G protein-coupled receptor binding, cell morphogenesis, and involved in pathways including metabolic process, proteoglycans in cancer. Top 10 hub genes with higher connectivity degree were selected for subsequent expression and prognosis analysis. After take expression levels and prognostic roles of hub genes and their upstream miRNAs and lncRNAs in OC into consideration, 2 mRNAs (TACC3 and CXCR4), 2 miRNAs (hsa-miR-425-5p and hsa-miR-146a-5p) and 3 lncRNAs (FUT8-AS1, LINC00665 and LINC01535) were significantly associated with the poor prognosis of OC. The mRNA-miRNA-lncRNA networks (TACC3-hsa-miR-425-5p-FUT8-AS1 and CXCR4-hsa-miR-146a-5p-LINC00665/LINC01535) were eventually constructed in OC based on ceRNA mechanism. Conclusion: We successfully constructed novel ceRNA network associated with the prognosis of ovarian cancer, which may provide a new strategy for early diagnosis and therapeutic intervention of OC.

Project description:BackgroundAbdominal aortic aneurysm (AAA) is a disease commonly seen in the elderly. The aneurysm diameter increases yearly, and the larger the AAA the higher the risk of rupture, increasing the risk of death. However, there are no current effective interventions in the early stages of AAA.MethodsFour gene expression profiling datasets, including 23 normal artery (NOR) tissue samples and 97 AAA tissue samples, were integrated in order to explore potential molecular biological targets for early intervention. After preprocessing, differentially expressed genes (DEGs) between AAA and NOR were identified using LIMMA package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were conducted using the DAVID database. The protein-protein interaction network was constructed and hub genes were identified using the STRING database and plugins in Cytoscape. A circular RNA (circRNA) profile of four NOR tissues versus four AAA tissues was then reanalyzed. A circRNA-miRNA-mRNA interaction network was constructed after predictions were made using the Targetscan and Circinteractome databases.ResultsA total of 440 DEGs (263 up-regulated and 177 down-regulated) were identified in the AAA group, compared with the NOR group. The majority were associated with the extracellular matrix, tumor necrosis factor-α, and transforming growth factor-β. Ten hub gene-encoded proteins (namely IL6, RPS27A, JUN, UBC, UBA52, FOS, IL1B, MMP9, SPP1 and CCL2) coupled with a higher degree of connectivity hub were identified after protein-protein interaction network analysis. Our results, in combination with the results of previous studies revealed that miR-635, miR-527, miR-520h, miR-938 and miR-518a-5p may be affected by circ_0005073 and impact the expression of hub genes such as CCL2, SPP1 and UBA52. The miR-1206 may also be affected by circ_0090069 and impact RPS27A expression.ConclusionsThis circRNA-miRNA-mRNA network may perform critical roles in AAA and may be a novel target for early intervention.

Dataset Information

Construction of lncRNA-miRNA-mRNA networks reveals functional lncRNAs in abdominal aortic aneurysm.

Publications

Construction of lncRNA-miRNA-mRNA networks reveals functional lncRNAs in abdominal aortic aneurysm.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets