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MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis.

ABSTRACT: Growing evidence indicates that microRNAs (miRNAs) have a key role in processes involved in type 1 diabetes mellitus (T1DM) pathogenesis, including immune system functions and beta-cell metabolism and death. Although dysregulated miRNA profiles have been identified in T1DM patients, results are inconclusive; with only few miRNAs being consistently dysregulated among studies. Thus, we performed a systematic review of the literature on the subject, followed by bioinformatic analysis, to point out which miRNAs are dysregulated in T1DM-related tissues and in which pathways they act. PubMed and EMBASE were searched to identify all studies that compared miRNA expressions between T1DM patients and non-diabetic controls. Search was completed in August, 2017. Those miRNAs consistently dysregulated in T1DM-related tissues were submitted to bioinformatic analysis, using six databases of miRNA-target gene interactions to retrieve their putative targets and identify potentially affected pathways under their regulation. Thirty-three studies were included in the systematic review: 19 of them reported miRNA expressions in human samples, 13 in murine models and one in both human and murine samples. Among 278 dysregulated miRNAs reported in these studies, 25.9% were reported in at least 2 studies; however, only 48 of them were analyzed in tissues directly related to T1DM pathogenesis (serum/plasma, pancreas and peripheral blood mononuclear cells (PBMCs)). Regarding circulating miRNAs, 11 were consistently dysregulated in T1DM patients compared to controls: miR-21-5p, miR-24-3p, miR-100-5p, miR-146a-5p, miR-148a-3p, miR-150-5p, miR-181a-5p, miR-210-5p, miR-342-3p, miR-375 and miR-1275. The bioinformatic analysis retrieved a total of 5867 validated and 2979 predicted miRNA-target interactions for human miRNAs. In functional enrichment analysis of miRNA target genes, 77 KEGG terms were enriched for more than one miRNA. These miRNAs are involved in pathways related to immune system function, cell survival, cell proliferation and insulin biosynthesis and secretion. In conclusion, eleven circulating miRNAs seem to be dysregulated in T1DM patients in different studies, being potential circulating biomarkers of this disease.

SUBMITTER: Assmann TS

PROVIDER: S-EPMC5682418 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis.

Assmann Taís S TS Recamonde-Mendoza Mariana M De Souza Bianca M BM Crispim Daisy D

Endocrine connections 20171006 8

Growing evidence indicates that microRNAs (miRNAs) have a key role in processes involved in type 1 diabetes mellitus (T1DM) pathogenesis, including immune system functions and beta-cell metabolism and death. Although dysregulated miRNA profiles have been identified in T1DM patients, results are inconclusive; with only few miRNAs being consistently dysregulated among studies. Thus, we performed a systematic review of the literature on the subject, followed by bioinformatic analysis, to point out ...[more]

PMID: 28986402

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Project description:Type 1 diabetes (T1D) is an autoimmune disease that is typically diagnosed in children. The aim of the present study was to identify potential genes involved in the pathogenesis of childhood T1D. Two datasets of mRNA expression in children with T1D were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) in children with T1D were identified. Functional analysis was performed and a protein‑protein interaction (PPI) network was constructed, as was a transcription factor (TF)‑target network. The expression of selected DEGs was further assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis. Electronic validation and diagnostic value analysis of the identified DEGs [cytokine inducible SH2 containing protein (CISH), SR‑related CTD associated factor 11 (SCAF11), estrogen receptor 1 (ESR1), Rho GTPase activating protein 25 (ARHGAP25), major histocompatibility complex, class II, DR β4 (HLA‑DRB4) and interleukin 23 subunit α (IL23A)] was performed in the GEO dataset. Compared with the normal control group, a total of 1,467 DEGs with P<0.05 were identified in children with T1D. CISH and SCAF11 were determined to be the most up‑ and downregulated genes, respectively. Heterogeneous nuclear ribonucleoprotein D (HNRNPD; degree=33), protein kinase AMP‑activated catalytic subunit α1 (PRKAA1; degree=11), integrin subunit α4 (ITGA4; degree=8) and ESR1 (degree=8) were identified in the PPI network as high‑degree genes. ARHGAP25 (degree=12), HNRNPD (degree=10), HLA‑DRB4 (degree=10) and IL23A (degree=9) were high‑degree genes identified in the TF‑target network. RT‑qPCR revealed that the expression of HNRNPD, PRKAA1, ITGA4 and transporter 2, ATP binding cassette subfamily B member was consistent with the results of the integrated analysis. Furthermore, the results of the electronic validation were consistent with the bioinformatics analysis. SCAF11, CISH and ARHGAP25 were identified to possess value as potential diagnostic markers for children with T1D. In conclusion, identifying DEGs in children with T1D may contribute to our understanding of its pathogenesis, and such DEGs may be used as diagnostic biomarkers for children with T1D.

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MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis.

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MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis.

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