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Identification of microRNA as sepsis biomarker based on miRNAs regulatory network analysis.

ABSTRACT: Sepsis is regarded as arising from an unusual systemic response to infection but the physiopathology of sepsis remains elusive. At present, sepsis is still a fatal condition with delayed diagnosis and a poor outcome. Many biomarkers have been reported in clinical application for patients with sepsis, and claimed to improve the diagnosis and treatment. Because of the difficulty in the interpreting of clinical features of sepsis, some biomarkers do not show high sensitivity and specificity. MicroRNAs (miRNAs) are small noncoding RNAs which pair the sites in mRNAs to regulate gene expression in eukaryotes. They play a key role in inflammatory response, and have been validated to be potential sepsis biomarker recently. In the present work, we apply a miRNA regulatory network based method to identify novel microRNA biomarkers associated with the early diagnosis of sepsis. By analyzing the miRNA expression profiles and the miRNA regulatory network, we obtained novel miRNAs associated with sepsis. Pathways analysis, disease ontology analysis, and protein-protein interaction network (PIN) analysis, as well as ROC curve, were exploited to testify the reliability of the predicted miRNAs. We finally identified 8 novel miRNAs which have the potential to be sepsis biomarkers.

SUBMITTER: Huang J

PROVIDER: S-EPMC3997997 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Identification of microRNA as sepsis biomarker based on miRNAs regulatory network analysis.

Huang Jie J Sun Zhandong Z Yan Wenying W Zhu Yujie Y Lin Yuxin Y Chen Jiajai J Shen Bairong B Wang Jian J

BioMed research international 20140406

Sepsis is regarded as arising from an unusual systemic response to infection but the physiopathology of sepsis remains elusive. At present, sepsis is still a fatal condition with delayed diagnosis and a poor outcome. Many biomarkers have been reported in clinical application for patients with sepsis, and claimed to improve the diagnosis and treatment. Because of the difficulty in the interpreting of clinical features of sepsis, some biomarkers do not show high sensitivity and specificity. MicroR ...[more]

PMID: 24809055

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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:BackgroundMicroRNA (miRNA) is a class of small RNAs of ~22nt which play essential roles in many crucial biological processes and numerous human diseases at post-transcriptional level of gene expression. It has been revealed that miRNA genes tend to be clustered, and the miRNAs organized into one cluster are usually transcribed coordinately. This implies a coordinated regulation mode exerted by clustered miRNAs. However, how the clustered miRNAs coordinate their regulations on large scale gene expression is still unclear.ResultsWe constructed the miRNA-transcription factor regulatory network that contains the interactions between transcription factors (TFs), miRNAs and non-TF protein-coding genes, and made a genome-wide study on the regulatory coordination of clustered miRNAs. We found that there are two types of miRNA clusters, i.e. homo-clusters that contain miRNAs of the same family and hetero-clusters that contain miRNAs of various families. In general, the homo-clustered as well as the hetero-clustered miRNAs both exhibit coordinated regulation since the miRNAs belonging to one cluster tend to be involved in the same network module, which performs a relatively isolated biological function. However, the homo-clustered miRNAs show a direct regulatory coordination that is realized by one-step regulation (i.e. the direct regulation of the coordinated targets), whereas the hetero-clustered miRNAs show an indirect regulatory coordination that is realized by a regulation comprising at least three steps (e.g. the regulation on the coordinated targets by a miRNA through a sequential action of two TFs). The direct and indirect regulation target different categories of genes, the former predominantly regulating genes involved in emergent responses, the latter targeting genes that imply long-term effects.ConclusionThe genomic clustering of miRNAs is closely related to the coordinated regulation in the gene regulatory network. The pattern of regulatory coordination is dependent on the composition of the miRNA cluster. The homo-clustered miRNAs mainly coordinate their regulation rapidly, while the hetero-clustered miRNAs exert control with a delay. The diverse pattern of regulatory coordination suggests distinct roles of the homo-clustered and the hetero-clustered miRNAs in biological processes.

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Identification of microRNA as sepsis biomarker based on miRNAs regulatory network analysis.

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Identification of microRNA as sepsis biomarker based on miRNAs regulatory network analysis.

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