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Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs.

ABSTRACT: BACKGROUND:Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis. METHODS:Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma. RESULTS:This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide). CONCLUSIONS:The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.

SUBMITTER: Liao Y

PROVIDER: S-EPMC6954528 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs.

Liao Yifang Y Li Ping P Wang Yanxia Y Chen Hong H Ning Shangwei S Su Dongju D

Respiratory research 20200110 1

<h4>Background</h4>Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential ...[more]

PMID: 31924195

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Project description:AimsThis study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network.MethodsExpression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs.ResultsWe detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA.ConclusionThe integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress.Cite this article: Bone Joint Res. 2020;9(3):90-98.

Project description:Long non?coding RNAs (lncRNAs) represent potential biomarkers for the diagnosis and treatment of various diseases; however, the role of circulating acute ischemic stroke (AIS)?related lncRNAs remains relatively unknown. The present study aimed to screen crucial lncRNAs for AIS based on the competing endogenous RNA (ceRNA) hypothesis. The expression profile datasets for one mRNA, accession no. GSE16561, and four microRNAs (miRNAs), accession nos. GSE95204, GSE86291, GSE55937 and GSE110993, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), lncRNAs (DELs), and miRNAs (DEMs) were identified, and ClusterProfiler was used to interpret the function of the DEGs. Based on the protein?protein interaction (PPI) network and module analyses, hub DEGs were identified. A ceRNA network was established based on miRNA?mRNA or miRNA?lncRNA interaction pairs. In total, 2,041 DEGs and 5 DELs were identified between the AIS and controls samples in GSE16561, and 10 DEMs between at least two of the four miRNA expression profiles. A PPI network was constructed with 1,235 DEGs, among which 20 genes were suggested to be hub genes. The hub genes paxillin (PXN), FYN?proto?oncogene, Src family tyrosine kinase (FYN), ras homolog family member A (RHOA), STAT1, and growth factor receptor?bound protein 2 (GRB2), were amongst the most significantly enriched modules extracted from the PPI network. Functional analysis revealed that these hub genes were associated with inflammation?related signaling pathways. An AIS?related ceRNA network was constructed, in which 4 DELs were predicted to function as ceRNAs for 9 DEMs, to regulate the five identified hub genes; that is, minichromosome maintenance complex component 3 associated protein?antisense RNA 1 (MCM3AP?AS1)/long intergenic non?protein coding RNA 1089 (LINC01089)/hsa?miRNA (miR)?125a/FYN, inositol?tetrakisphosphate 1?kinase?antisense RNA 1 (ITPK1?AS1)/hsa?let?7i/RHOA/GRB2/STAT1, and human leukocyte antigen complex group 27 (HCG27)/hsa?-miR?19a/PXN interaction axes. In conclusion, MCM3AP?AS1, LINC01089, ITPK1?AS1, and HCG27 may represent new biomarkers and underlying targets for the treatment of AIS.

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Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs.

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Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs.

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