Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis

ABSTRACT: Background: Psoriasis is a systemic inflammatory skin disease. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that recently have been found in the blood to be relevant as disease biomarkers. Objective: We aimed to explore miRNAs potential as blood biomarkers for psoriasis. Methods: Using microarray and quantitative real-time PCR we measured the global miRNA expression in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) from patients with psoriasis and healthy controls. Results: We identified several deregulated miRNAs in the blood from patients with psoriasis including miR-223 and miR-143 which were found to be significantly upregulated in the PBMCs from patients with psoriasis compared with healthy controls (FCH=1.63, P<0.01; FCH=2.18, P<0.01, respectively). In addition, miR-223 and miR-143 significantly correlated with the PASI score (r = 0.46, P<0.05; r=0.55, P<0.02, respectively). Receiver-operating characteristic analysis (ROC) showed that miR-223 and -143 have the potential to distinguish between psoriasis and healthy controls (miR-223: Area under the curve (AUC) = 0.80, miR-143: AUC = 0.75). Interestingly, after 3-5 weeks of treatment with methotrexate following a significant decrease in psoriasis severity, miR-223 and miR-143 were significantly downregulated in the PBMCs from patients with psoriasis. Conclusion: We suggest that changes in the miR-223 and miR-143 expressions in PBMCs from patients with psoriasis may serve as novel biomarkers for disease activity in psoriasis; however, further investigations are warranted to clarify their specific roles. In the present study, we compared the global miRNA expression profile between whole blood samples obtained from 24 patients with psoriasis (5 samples were excluded due to poor quality control) compared with 15 healthy controls.

ORGANISM(S): Homo sapiens

SUBMITTER: Marianne Løvendorf

PROVIDER: E-GEOD-55515 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis.

Løvendorf Marianne B MB Zibert John R JR Gyldenløve Mette M Røpke Mads A MA Skov Lone L

Journal of dermatological science 20140521 2

<h4>Background</h4>Psoriasis is a systemic inflammatory skin disease. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that recently have been found in the blood to be relevant as disease biomarkers.<h4>Objective</h4>We aimed to explore miRNAs potential as blood biomarkers for psoriasis.<h4>Methods</h4>Using microarray and quantitative real-time PCR we measured the global miRNA expression in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) from patients with pso ...[more]

PMID: 24909097

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Project description:In this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified ‘signature miRNAs’ in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated. Dysregulation in expression of microRNAs (miRNAs) in various tissues has been linked to a wide spectrum of diseases, including Type 2 Diabetes mellitus (T2D). In this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified ‘signature miRNAs’ in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated. Using luciferase assay, we further demonstrated that miR-144 directly targets IRS1 and showed its effects on protein expression via immunocytochemistry. From this cross-sectional study in humans, we have identified signature miRNAs which could explain the pathogenesis of T2D. Whether miRNAs like miR-144 could be potential therapeutic targets for management of T2D will need to be explored by further mechanistic and functional studies. Total RNA (plus miRNAs) was isolated using a modification of the RiboPure™-Blood kit from Ambion (Austin,TX) according to the manufacturer’s protocol. The concentration of total RNA and integrity were determined by using Nano-Drop ND-1000 Spectrophotometry (NanoDrop Tech, Rockland, Del) and gel electrophoresis respectively.

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Dataset Information

MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis

Publications

MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis.

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