Dataset Information

Integrated micro/messenger RNA regulatory networks in essential thrombocytosis.

ABSTRACT: Essential thrombocytosis (ET) is a chronic myeloproliferative disorder with an unregulated surplus of platelets. Complications of ET include stroke, heart attack, and formation of blood clots. Although platelet-enhancing mutations have been identified in ET cohorts, genetic networks causally implicated in thrombotic risk remain unestablished. In this study, we aim to identify novel ET-related miRNA-mRNA regulatory networks through comparisons of transcriptomes between healthy controls and ET patients. Four network discovery algorithms have been employed, including (a) Pearson correlation network, (b) sparse supervised canonical correlation analysis (sSCCA), (c) sparse partial correlation network analysis (SPACE), and, (d) (sparse) Bayesian network analysis-all through a combined data-driven and knowledge-based analysis. The result predicts a close relationship between an 8-miRNA set (miR-9, miR-490-5p, miR-490-3p, miR-182, miR-34a, miR-196b, miR-34b*, miR-181a-2*) and a 9-mRNA set (CAV2, LAPTM4B, TIMP1, PKIG, WASF1, MMP1, ERVH-4, NME4, HSD17B12). The majority of the identified variables have been linked to hematologic functions by a number of studies. Furthermore, it is observed that the selected mRNAs are highly relevant to ET disease, and provide an initial framework for dissecting both platelet-enhancing and functional consequences of dysregulated platelet production.

SUBMITTER: Zhao L

PROVIDER: S-EPMC5805260 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Integrated micro/messenger RNA regulatory networks in essential thrombocytosis.

Zhao Lu L Wu Song S Huang Erya E Gnatenko Dimitri D Bahou Wadie F WF Zhu Wei W

PloS one 20180208 2

Essential thrombocytosis (ET) is a chronic myeloproliferative disorder with an unregulated surplus of platelets. Complications of ET include stroke, heart attack, and formation of blood clots. Although platelet-enhancing mutations have been identified in ET cohorts, genetic networks causally implicated in thrombotic risk remain unestablished. In this study, we aim to identify novel ET-related miRNA-mRNA regulatory networks through comparisons of transcriptomes between healthy controls and ET pat ...[more]

PMID: 29420626

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Project description:Background Circular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF). Methods The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs. Results A total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. Conclusion We speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.

Project description:BackgroundPatients with non-small cell lung cancer (NSCLC) are diagnosed in advanced stages and with a poor 5-year survival rate. There is a critical need to identify novel biomarkers to improve the therapy and overall prognosis of this disease.MethodsDifferentially expressed genes (DEGs) were identified from three profiles of GSE101586, GSE101684 and GSE112214 using Venn diagrams. hsa_circ_0043256 were validated using quantitative real-time polymerase chain reaction (RT-qPCR). The circular RNA-microRNA-messenger RNA (circRNA-miRNA-mRNA) regulatory network was constructed with Cytoscape 3.7.0. Hub genes were identified with protein interaction (PPI) and validated with the Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA) databases, and immunohistochemistry. Survival analyses were also performed using a Kaplan-Meier (KM) plotter. The effects of hsa_circ_0043256 on cell proliferation and cell cycles were evaluated by EdU staining and flow cytometry, respectively.Resultshsa_circ_0043256, hsa_circ_0029426 and hsa_circ_0049271 were obtained. Following RT-qPCR validation, hsa_circ_0043256 was selected for further analysis. In addition, functional experiment results indicated that hsa_circ_0043256 could inhibit cell proliferation and cell-cycle progression of NSCLC cells in vitro. Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated DEGs might be associated with lung cancer onset and progression. A PPI network based on the 209 genes was established, and five hub genes (BIRC5, SHCBP1, CCNA2, SKA3, and GINS1) were determined. Following verification of five hub genes using GEPIA database, HPA database, and immunohistochemistry. High expression of all five hub genes led to poor overall survival.ConclusionOur study constructed a circRNA-miRNA-mRNA network of hsa_circ_0043256. hsa_circ_0043256 may be a potential therapeutic target for lung cancer.

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Integrated micro/messenger RNA regulatory networks in essential thrombocytosis.

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Integrated micro/messenger RNA regulatory networks in essential thrombocytosis.

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