ABSTRACT
Objective:To explore the potential Hub genes, key miRNAs, biological processes and related signaling pathways in the pathogenesis of osteoarthritis (OA), and provide bioinformatics basis for the pathogenesis and treatment of OA.Methods:The expression profiling chip of OA synovial tissue sample from Gene Expression Omnibus (GEO) were downloaded, differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction network (PPI) was constructed. STRING and Cytoscape was used for module analysis, and the Hub gene was further identified, and further miRNAs mining of the Hub gene was carried out.Results:Finally, 9 Hub genes (SOCS3, BTRC, FBXO32, KLHL22, UBE3A, HUWE1, UBR4, ANAPC5, TRIM50) and 2 key miRNAs (hsa-miR-103a-3P, hsa-miR-107) related to the progression of OA were identified .They might be potential biomarkers for the pathogenesis of OA. We also found that signal transduction, the transcriptional positive regulation of RNA polymerase Ⅱ promoter, and protein serine/threoninase activity had a certain correlation with the pathogenesis of OA. In addition, our analysis results showed that cAMP signaling pathway and Rap1 signaling pathway were also involved in the progression of OA.Conclusion:The potential biological molecules, biological processes and related pathways identified in this study may guide us for the further research on the etiology and treatment of OA.
ABSTRACT
Objective To examine the expression of miR-210,miR-155 and miR-34a in the peripheral blood of patients with systemic lupus erythematosus (SLE) and to analyze their clinical significance.Methods One hundred and teenty-six SLE patients were divided into the stable group (n=35),mild active group (n=49),medium and severe active group (n =42) based on systemic lupus erythematosus disease activity index (SLEDAI) score.Meanwhile,40 subjects for healthy check-up were selected as controls.The clinical data of patients were collected.Complete blood count,liver and kidney function and immunological indexes were tested in patients and the lupus activity index was assessed.The expression level of miR-210,miR-155 and miR-34a were determined by real-time polymerase chain reaction.Furthermore,the correlation between their levels and clinical parameters such as erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),SLEDAI score,were analyzed.The expression levels of miR-210,miR-155 and miR-34a in each group were compared by one-way analysis of variance (ANOVA).Correlation analysis was performed by non parametric Spearman test.The difference was statistically significant if P＜0.05.The diagnostic value of SLE was evaluated by the subjects characteristic (ROC) curve.Results The levels of miR-210 and miR-155 were no significantly differencet between the stable group (0.017±0.012);(0.150±0.101) and the control group (0.015±0.010);(0.071±0.034),but they were increased in mild active group (0.502±0.166);(1.521±1.138),medium and severe active group(1.237±0.584),(13.589±9.827) (F=124.321,70.065,P＜0.05).The average expression level of miR-34a in the control group,the stable group,the mild active group and the moderate and severe active group were (0.005±0.003),(0.249±0.137),(2.981±1.762) and (9.625±5.873) respectively,and showed a trend of increase in turn (F=75.688,P＜0.05).The expression level of miR-210,miR-155 and miR-34a was not significantly different between the LN group and the non LN group (P＞0.05).The R values of miR-210,miR-155,miR-34a and each index were IgG (0.347;0.518;0.482);IgA (0.463;0.635;0.379);IgM (0.287;0.392;0.336),ESR(0.317;0.428;0.369),C3(0.243;0.429;0.381),C4(0.317;0.513;0.429),ANA titer (0.462;0.594;0.527),Anti-ds-DNA antibodies (0.391;0.586;0.483),SLEDAI scores (-0.412;-0.558;-0.493),and there were significant correlations (P＜0.05).In patients with SLE,there was no significant correlation between hormone therapy alone or hormone plus immunosuppressive therapy (P＞0.05).The sensitivity and specificity of miR-210,miR-155,miR-34a in combination for the diagnosis of SLE reached 75.7％ and 72.3％,respectively.Conclusion The levels of miR-210,miR-155 and miR-34a in combination may be used as bio-markers for the diagnosis of SLE.