The interaction between genes and the environment in psoriasis is firmly coupled by epigenetic modification. Epigenetic modifications are inherited variations in gene expression devoid of DNA sequence alterations. Non-coding RNAs are regarded as one of the epigenetic modifications that lead eventually to enduring heritable variations in gene expression. In the present study, we chose the lncRNA, Psoriasis-susceptibility-Related RNA Gene Induced by Stress (PRINS) known to have a regulatory role in psoriasis and deduced its axis of lncRNA-miRNA-mRNA through an in silico data analysis. We aimed to assess the expression levels of this lncRNA-miRNA-mRNA in patients with psoriasis to elucidate their possible roles in psoriasis management. We investigated the lncRNA-PRINS and its target microRNAs (miRNA124-3p, miRNA203a-5p, miRNA129-5p, miRNA146a-5p, miRNA9-5p) and partner genes (NPM, G1P3) expression levels in the plasma of 120 patients with psoriasis compared to 120 healthy volunteers using quantitative real-time polymerase chain reaction and correlated the results with the patients’ clinicopathological data. Finally, we performed a function, disease, and pathway enrichment analysis for the LncRNA-miRNA-mRNA axis under study. The lncRNA PRINS, G1P3, and NPM genes showed significantly under-expressed levels while all miRNAs included in the study showed significant over-expression in patients with psoriasis relative to controls. The lncRNA PRINS, G1P3, and NPM genes showed a significant direct correlation with each other and inverse significant correlations with all miRNAs under study. All the study biomarkers showed significant results for discriminating between patients with psoriasis and controls using a receiver operating curve analysis with sensitivity over 90% except for PRINS, which was 74.2%. The G1P3 gene showed a direct significant correlation with body mass index in patients with psoriasis (p = 0.009) and an inverse significant correlation with age (p = 0.034). The NPM gene showed a significant correlation with body mass index in patients with psoriasis (p = 0.002). Based on our results, we suggest that restoring the altered PRINS-miRNA-mRNA axis gene expression levels might represent a tool to prevent psoriasis worsening, along with standard therapy. Thus, on the clinical practice level, the PRINS-miRNA-mRNA axis expression profile can be utilized in designing specific targeted therapy aimed at applying a personalized medicine approach among patients with psoriasis.
Abstract Background Circulating microRNAs (miRNAs) are considered a hot spot of research that can be employed for monitoring and/or diagnostic purposes in coronary artery disease (CAD). Since different disease features might be reflected on altered profiles or plasma miRNAs concentrations, a combination of miRNAs can provide more reliable non-invasive biomarkers for CAD. Subjects and methods We investigated a panel of 14-miRNAs selected using bioinformatics databases and current literature searching for miRNAs involved in CAD using quantitative real-time PCR technique in 73 CAD patients compared to 73 controls followed by function and pathway enrichment analysis for the 14-miRNAs. Results Our results revealed three out of the 14 circulating miRNAs understudy; miRNAs miR133a, miR155 and miR208a were downregulated. While 11 miRNAs were up-regulated in a descending order from highest fold change to lowest: miR-182, miR-145, miR-21, miR-126, miR-200b, miR-146A, miR-205, miR-135b, miR-196b, miR-140b and, miR-223. The ROC curve analysis indicated that miR-145, miR-182, miR-133a and, miR-205 were excellent biomarkers with the highest AUCs as biomarkers in CAD. All miRNAs under study except miR-208 revealed a statistically significant relation with dyslipidemia. MiR-126 and miR-155 showed significance with BMI grade, while only miR-133a showed significance with the obese patients in general. MiR-135b and miR-140b showed a significant correlation with the Wall Motion Severity Index. Pathway enrichment analysis for the miRNAS understudy revealed pathways relevant to the fatty acid biosynthesis, ECM-receptor interaction, proteoglycans in cancer, and adherens junction. Conclusion The results of this study identified a differentially expressed circulating miRNAs signature that can discriminate CAD patients from normal subjects. These results provide new insights into the significant role of miRNAs expression associated with CAD pathogenesis.
Abstract: In autoimmune illnesses like Rheumatoid Arthritis (RA), the synovium is constantly inflamed, and joints are ruptured. It is becoming increasingly clear that stem cells, especially notably mesenchymal stem cells (MSCs) and microRNAs (miRNAs), play important roles in the onset and amelioration of RA. There is mounting evidence from both animal and human studies that suggests a potentially safe and effective method to treat RA and other intractable diseases by reducing chronic inflammation and spurring tissue regeneration through the transplantation of multipotent adult stem cells, such as mesenchymal stromal/stem cells. To control gene expression, which impacts immune cell differentiation and inflammatory pathways, microRNAs (miRNAs) are crucial, even though MSCs can self-renew and modify inflammatory reactions. The pathophysiology of RA is marked by the dysregulation of immunological responses and the proliferation of fibroblast-like synoviocytes, which are linked to the aberrant expression of specific microRNAs (miRNAs). This study mainly aims to examine the therapeutic implications of these microRNAs (miRNAs) in relation to RA, as they can function as diagnostic and prognostic indicators. This study explores the functions of microRNAs (miRNAs) and stem cells in rheumatoid arthritis (RA), drawing attention to the relevance of these biological processes and the potential for creating novel therapeutic strategies to improve patient outcomes.
Numerous microRNAs (miRNAs) have been found to have an aberrant expression in the peripheral blood or psoriasis patients' lesions. Psoriasis was shown to have the abnormal expression of microRNA-203 (miR-203). It is a skin-specific signal that governs cellular proliferation in a protein kinase C-dependent manner and is mostly generated by keratinocytes. This work evaluated the expression levels of the circulating miR-203 target genes SOCS3, SOCS6, TP63, TNF-, IL8, and IL24 in psoriasis patients. Using a relative quantitation PCR technique, we determined the expression levels of miR-203 and its target genes (SOCS3, SOCS6, TP63, TNF-, IL8, and IL24) in the plasma of 120 psoriatic patients and matched healthy controls. The disease characteristics of the patients were then correlated with the expression results. We also conducted numerous enrichment analyses for the diseases, functions, and pathways connected to the under-researched biomarkers. Compared to healthy controls, psoriatic patients had significantly increased levels of miR-203 expression; 7.1 (4.4-9.9). In contrast, psoriatic patients had significantly lower expression of all the examined genes compared to healthy controls. Regarding all the study biomarkers, the receiver operating characteristic (ROC) curve analysis demonstrated significant sensitivity and specificity for differentiating between psoriatic patients and healthy controls. According to the results of the disease matching score generated by miR-203 and its target genes, psoriasis was ranked first with a score of 4.45. The third-place finisher with a value of 3.98, it also demonstrated that miR-203 and its target genes are connected to various skin disorders. Our results show that miR-203 contributes to psoriasis pathogenesis not only locally in skin lesions but also in circulation, indicating that it may contribute to the systemic symptoms of the illness. MiR-203 overexpression in psoriasis suggests that miR-203 may be involved in an anti-inflammatory response because it targets both SOCS gene family members and pro-inflammatory cytokines.
Background: Vitiligo is the most common skin disorder of depigmentation and is a multi-hypothesis disease requiring multifaceted interaction between autoimmune, biochemical, and genetic hypotheses. MiRNAs; are a major class of tiny noncoding RNAs. MiR-320 regulates inflammatory cytokines IL-2, IL-17, IFN-γ, and CXCL9 which are the main inflammatory cytokines contributing to the etiopathogenesis of vitiligo. Aim: To measure serum levels of miR-320 in vitiligo patients compared with controls to highlight the possible association of miR-320 with pathogenesis and severity of vitiligo. Subjects and Methods: A case-control study included 2 groups: group 1 involved 99 vitiligo patients; group 2 involved 99 healthy volunteers matched for age and sex. Disease activity and severity were assessed for each patient by VIDA and VASI scores. Serum miR-320 levels were assessed as blood samples were obtained from each patient and control than a quantitative measure of miRNA-320, using quantitative real-time PCR assay was done on all samples. Results: The mean level of miR-320 among patients was 23.05 ± 83.21; the mean level of miR-320 among controls was 1.0 ± 0.0. The variance between both groups was statistically significant (P < 0.05). Expression levels of miR-320 in vitiligo patients were higher than controls as a median of miR-320 levels in vitiligo patients was upregulated, being 3.19-fold higher than levels detected in controls. Conclusion: Serum miR-320 level was overexpressed in vitiligo patients compared to controls. Moreover, there was an insignificant association between miR-320 serum level and disease severity. Thus, miR-320 might have a key role in the etiopathogenesis of vitiligo.
Complement system has a very important role in our defense against different pathogens and harmful immune complexes.The lectin pathway of complement system is activated by mannose binding lectin leading to complement cascade ending with the removal of these invading pathogens and the injuring immune complexes.Defects in mannose binding lectin were found to be associated with MBL2 gene polymorphisms such as exon 1 polymorphisms and promotor region polymorphisms.These defects were linked to serious autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.The aim of our review is to provide an overview of mannose binding lectin role in complement system and to outline the information about mannose binding lectin defects with systemic lupus erythematosus and rheumatoid arthritis in addition to the possible related explanations.Mannose binding lectin variants were believed to have an association with these autoimmune disorders by many studies with the presence of conflicted studies as well.