Dataset Information

Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy.

ABSTRACT: OBJECTIVE:To evaluate the expression of a set of miRNAs to identify differentially expressed miRNAs that might be considered reliable biomarkers on Diabetic Retinopathy (DR) blood samples. RESULTS:Expression levels of MiR-320a, MiR-342-3p, MiR-155, MiR-99a, MiR-29a and MiR-27b were analyzed in 60 healthy controls, 48 Diabetes Melitus (DM) without DR patients and 62 DR patients by qRT-PCR. MiR-320a was shown to be downregulated in the plasma of DR patients compared with DM patients without DR and healthy subjects. Target genes were predicted using miRWalk3.0, miR targeting data and target gene interaction data were imported to Cytoscape to visualize and merge networks and top ranked predicted genes were run through Ontology Genes to perform enrichment analysis on gene sets and classification system to identify biological processes and reactome pathways associated with DR. Highly scored target genes of miR-320a were categorized for various biological processes, including negative regulation of cell aging, negative regulation of cellular protein metabolic process and regulation of cellular response to stress that are critical to the development of DR. Our findings suggest that MiR-320a may have a role in the pathogenesis of DR and may represent novel biomarkers for this disease.

SUBMITTER: Prado MSG

PROVIDER: S-EPMC7077016 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy.

Prado Marcelle SanJuan Ganem MSG de Jesus Mirthz Lemos ML de Goes Thaline Cunha TC Mendonça Lucilla Silva Oliveira LSO Kaneto Carla Martins CM

BMC research notes 20200316 1

<h4>Objective</h4>To evaluate the expression of a set of miRNAs to identify differentially expressed miRNAs that might be considered reliable biomarkers on Diabetic Retinopathy (DR) blood samples.<h4>Results</h4>Expression levels of MiR-320a, MiR-342-3p, MiR-155, MiR-99a, MiR-29a and MiR-27b were analyzed in 60 healthy controls, 48 Diabetes Melitus (DM) without DR patients and 62 DR patients by qRT-PCR. MiR-320a was shown to be downregulated in the plasma of DR patients compared with DM patients ...[more]

PMID: 32178730

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Project description:BackgroundAccumulating evidence has suggested a link between adipokines and diabetic retinopathy (DR). This study is aimed at investigating the risk factors for sight-threatening DR (STDR) and establishing a prognostic model for predicting STDR among a high-risk population of patients with type 2 diabetes mellitus (T2DM).MethodsPlasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. In the case-control set, principal component analysis (PCA) was performed to select optimal predictive cytokines for STDR, involving severe nonproliferative DR (NPDR) and proliferative DR. Support vector machine (SVM) was used to examine the possible combination of baseline plasma adipokines to discriminate the patients with mild NPDR who will later develop STDR. An individual prospective cohort with a follow-up period of 3 years was used for the external validation.ResultsIn both training and testing sets, involving 306 patients with T2DM, median levels of plasma adiponectin (APN), leptin, and fatty acid-binding protein 4 (FABP4) were significantly higher in the STDR group than those in mild NPDR. Except for adipsin, the other three adipokines, FABP4, APN, and leptin, were selected by PCA and integrated into SVM. The accuracy of the multivariate SVM classification model was acceptable in both the training set (AUC = 0.81, sensitivity = 71%, and specificity = 91%) and the testing set (AUC = 0.77, sensitivity = 61%, and specificity = 92%). 110 T2DM patients with mild NPDR, the high-risk population of STDR, were enrolled for external validation. Based on the SVM, the risk of each patient was calculated. More STDR occurred in the high-risk group than in the low-risk group, which were grouped by the median value of APN, FABP4, and leptin, respectively. The model was validated in an individual cohort using SVM with the AUC, sensitivity, and specificity reaching 0.77, 64%, and 91%, respectively.ConclusionsAdiponectin, leptin, and FABP4 were demonstrated to be associated with the severity of DR and maybe good predictors for STDR, suggesting that adipokines may play an important role in the pathophysiology of DR development.

Project description:Novel biomarkers for personalizing anticoagulation remain undetermined. We aimed to investigate the association of plasma miRNAs with pharmacokinetic-pharmacodynamic (PK-PD) profiles of rivaroxaban. This is a multicenter, exploratory study of miRNAs in a Chinese population. Healthy volunteers and patients receiving rivaroxaban were enrolled in the study. The area under the plasma concentration-time curve from time 0-t h (AUC0-t) and anti-Xa activity at 3 h (AXA3h) were measured in healthy volunteers, and AXA3h was measured in patients. MiRNAs were detected by miRNA microarray in 26 healthy volunteers with 20 mg rivaroxaban, and quantitative reverse transcription polymerase chain reaction was used to exclude undetectable ones. MiR-320a-3p and miR-483-5p were then quantified in 65 healthy volunteers and 71 patients. MiRNA levels at 3 h were compared between high and low AXA3h or AUC0-t subjects and in matched patients with or without bleeding during follow-up. The miRNA targets were predicted by TargetScan, miRTarBase, and miRDB. Validated genes were included in GO enrichment and KEGG analyses. The protein-protein interaction network was established by STRING and visualized by Cytoscape. A total of 136 Chinese subjects completed the study. In healthy volunteers taking 15 mg rivaroxaban, the miR-320a level at 3 h was significantly positively correlated with AXA3h and AUC0-t (r = 0.359, p = 0.025; r = 0.370, p = 0.02, respectively). A positive correlation was also observed between miR-483 and AXA3h or AUC0-t (r = 0.372, p = 0.02; r = 0.523, p = 0.001, respectively). MiR-320a and miR-483 levels at 3 h in the higher AUC0-t group were significantly higher than those at 0 h. MiR-483 levels at 3 h may distinguish healthy volunteers with high or low AXA3h or AUC0-t. In the 10 mg fed subgroup, higher 3 h mir-483 levels were also observed compared with the control group. No significant differences were found in the comparisons among patients. Bioinformatic analysis showed that these miRNAs may play a regulatory role by targeting ABCG2, ITGB3, PTEN, MAPK1/3, etc. CONCLUSIONS: MiR-320a and miR-483 levels were found to be associated with PK and PD profiles of rivaroxaban in healthy Chinese subjects. Further studies are required to verify these findings and explore the mechanisms.

Dataset Information

Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy.

Publications

Downregulation of circulating miR-320a and target gene prediction in patients with diabetic retinopathy.

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