Identification and bioinformatics analysis of lncRNAs in serum of patients with ankylosing spondylitis
Ontology highlight
ABSTRACT:
SUBMITTER: Kou J
PROVIDER: S-EPMC11017588 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundLong non-coding RNAs (lncRNAs) are important regulators in ankylosing spondylitis (AS). Few studies have examined the lncRNA-RNA binding protein (RBP) interaction in AS. This study performed bioinformatics analysis and clinical verification to identify key lncRNAs and propose their RBP interaction.MethodsThree GEO datasets of AS were analyzed by differential expression analysis. The differentially expressed lncRNAs between the AS and control groups were screened out, and the intersecting lncRNAs were regarded as target lncRNAs. Functional was performed to identify target lncRNAs by enrichment analysis, co-expressed RNA analysis, and lncRNA-RBP interaction analysis. Finally, this study analyzed the differential expression level and clinical value of lncRNAs between the AS and control groups.ResultsLinc00304, linc00926, and MIAT were differentially expressed and upregulated. Enrichment analysis indicated that the key KEGG terms were the T-cell receptor signaling pathway and B-cell receptor signaling pathway. The key molecular function term was protein binding, and the key biological process term was adaptive immune response. In qRT-PCR results, 44 samples were validated. linc00304 expression was positively correlated with bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). linc00926 expression was only positively correlated with ESR, whereas MIAT expression was positively correlated with BASFI, ESR, and CRP. Logistic regression revealed that linc00304, ESR, and CRP were the independent risk factors for BASDAI activation. The area under the curve (AUC) of serum linc00304 level in the diagnosis of AS was 0.687 (cutoff value: 0.413, specificity: 0.423, sensitivity: 0.900). AUC of linc00926 was 0.664 (cutoff value: 0.299, sensitivity: 0.882, specificity: 0.417). AUC of MIAT was 0.623 (cutoff value: 0.432, specificity: 0.443, sensitivity: 0.890) (all P <0.05).ConclusionOverall, this study uncovered three novel lncRNAs, which were upregulated in AS, and proposed a new lncRNA-RBP-mRNA interaction that might regulate adaptive immune response.
| S-EPMC9642369 | biostudies-literature
Project description:We randomly selected three serum samples each from an AS and a normal control (NC) group for high-throughput sequencing followed by using edgeR to find differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway analyses and gene set enrichment analysis (GSEA)were used to comprehensively analyze the possible functions and pathways involved with these DEGs. Protein–protein interaction (PPI) networks were constructed using the STRING database and Cytoscape. The modules and hub genes of these DEGs were identified using MCODE and CytoHubba plugins. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression levels of candidate genes in serum samples from AS patients and healthy controls.
2022-10-16 | GSE205812 | GEO
Project description:ObjectiveThe aim of this study was to search for key genes in ankylosing spondylitis (AS) through comprehensive bioinformatics analysis, thus providing some theoretical support for future diagnosis and treatment of AS and further research.MethodsGene expression profiles were collected from Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ) by searching for the term "ankylosing spondylitis". Ultimately, two microarray datasets (GSE73754 and GSE11886) were downloaded from the GEO database. A bioinformatic approach was used to screen differentially expressed genes and perform functional enrichment analysis to obtain biological functions and signalling pathways associated with the disease. Weighted correlation network analysis (WGCNA) was used to further obtain key genes. Immune infiltration analysis was performed using the CIBERSORT algorithm to conduct a correlation analysis of key genes with immune cells. The GWAS data of AS were analysed to identify the pathogenic regions of key genes in AS. Finally, potential therapeutic agents for AS were predicted using these key genes.ResultsA total of 7 potential biomarkers were identified: DYSF, BASP1, PYGL, SPI1, C5AR1, ANPEP and SORL1. ROC curves showed good prediction for each gene. T cell, CD4 naïve cell, and neutrophil levels were significantly higher in the disease group than in the paired normal group, and key gene expression was strongly correlated with immune cells. CMap results showed that the expression profiles of ibuprofen, forskolin, bongkrek-acid, and cimaterol showed the most significant negative correlation with the expression profiles of disease perturbations, suggesting that these drugs may play a role in AS treatment.ConclusionThe potential biomarkers of AS screened in this study are closely related to the level of immune cell infiltration and play an important role in the immune microenvironment. This may provide help in the clinical diagnosis and treatment of AS and provide new ideas for further research.
| S-EPMC10207833 | biostudies-literature
Project description:BackgroundAnkylosing spondylitis (AS) is a chronic autoimmune disease affecting the sacroiliac joint. To date, few studies have examined the association between long non-coding RNAs (lncRNAs) and AS pathogenesis. As such, we herein sought to characterize patterns of AS-related lncRNA expression and to evaluate the potential role played by these lncRNAs in this complex autoimmune context.MethodsWe conducted a RNA-seq analysis of peripheral blood mononuclear cell (PBMC) samples isolated from five AS patients and corresponding controls. These data were then leveraged to characterize AS-related lncRNA expression patterns. We further conducted GO and KEGG enrichment analyses of the parental genes encoding these lncRNAs, and we confirmed the validity of our RNA-seq data by assessing the expression of six lncRNAs via qRT-PCR in 15 AS and control patient samples. Pearson correlation analyses were additionally employed to examine the associations between the expression levels of these six lncRNAs and patient clinical index values.ResultsWe detected 56,575 total lncRNAs in AS and control patient samples during our initial RNA-seq analysis, of which 200 and 70 were found to be up- and down-regulated (FC > 2 or < 0.05; P < 0.05), respectively, in AS samples relative to controls. In qRT-PCR validation assays, we confirmed the significant upregulation of NONHSAT118801.2, ENST00000444046, and NONHSAT183847.1 and the significant downregulation of NONHSAT205110.1, NONHSAT105444.2, and NONHSAT051856.2 in AS patient samples. We further found the expression of NONHSAT118801.2 and NONHSAT183847.1 to be positively correlated with disease severity.ConclusionOverall, our findings highlight several lncRNAs that are specifically expressed in PBMCs of AS patients, indicating that they may play key functions in the pathogenesis of this autoimmune disease. Specifically, we determined that NONHSAT118801.2 and NONHSAT183847.1 may influence the occurrence and development of AS.
| S-EPMC7955637 | biostudies-literature
Project description:The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis-related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms-least absolute shrinkage and selection operation, support vector machine-recursive feature elimination and random forest-two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory-activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory-resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory-resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune-related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies.
| S-EPMC11258886 | biostudies-literature
Project description:Recent studies have reported that circular RNAs (circRNAs) play a crucial regulatory role in a variety of human diseases. However, the roles of circRNAs in MSC osteogenesis in ankylosing spondylitis (AS) remain unclear. these results revealed the expression profiles of miRNAs and the potential functions of the DE miRNAs in the MSC of patients with AS, which may provide new clues for understanding the mechanisms of ossify associated with AS, and proceed to identify novel potential molecular targets for the diagnoses and treatment of AS.
2022-05-20 | GSE203155 | GEO
Project description:ObjectivesThe aim of this study was to investigate the activities of serum paraoxonase and arylesterase in patients with ankylosing spondylitis with respect to those of healthy controls, to assess whether these enzyme levels are related to disease activity and functional capacity.MethodsThe study included 32 patients with ankylosing spondylitis whose diagnoses were made according to the modified New York criteria as well as 25 healthy controls matched for age and sex. The Bath Ankylosing Spondylitis Disease Activity Index and the Bath Ankylosing Spondylitis Functional Index were applied to the ankylosing spondylitis patients. As laboratory parameters, the erythrocyte sedimentation rate and serum C-reactive protein level were measured in patients and control subjects. Paraoxonase and arylesterase enzyme activities were measured using appropriate methods.ResultsNo statistically significant differences (p>0.05) were found between the ankylosing spondylitis patients and controls in terms of serum paraoxonase or arylesterase levels. Furthermore, there was no correlation between clinical and laboratory parameters in patients with ankylosing spondylitis.ConclusionSerum paraoxonase and arylesterase levels in ankylosing spondylitis patients may not differ from those of healthy controls, and there is no significant correlation between antioxidant parameters and the Bath Ankylosing Spondylitis Disease Activity Index or Bath Ankylosing Spondylitis Functional Index scores in ankylosing spondylitis patients. Further research is needed to provide deeper understanding of this disease.
| S-EPMC2827704 | biostudies-literature
Project description:According to the results of the first genome-wide association study of ankylosing spondylitis (AS), endoplasmic reticulum aminopeptidase 1 (ERAP1) may serve an important role. However, a number of case-control studies have not been able to replicate this result using the same genetic markers. In the present study, the role of common genetic variants of ERAP1 in AS was investigated using two-stage bioinformatics analysis. In the first stage, a classical meta-analysis was performed to assess AS susceptibility markers in ERAP1 using data from available published case-control association studies. The summary odds ratios for 10 single nucleotide polymorphisms (SNPs) were observed to be statistically significant in different studies. In the second stage, the functional effects of these genetic ERAP1 variants were investigated using prediction tools and structural analyses. The K528R (rs30187) substitution SNP in ERAP1 was termed as likely damaging by PolyPhen-2 software, was observed to be located close to the entrance of the substrate pocket, and was predicted to contribute to reduced ERAP1 aminopeptidase activity. In addition, the R725Q (rs17482078) SNP, which was an additional potentially damaging substitution, was suggested to decrease the enzymatic activity of ERAP1, as this substitution may lead to the loss of two hydrogen bonds between R725 and D766 and affect the stability of the C-terminus of ERAP1. In conclusion, the results of the two-stage bioinformatics analysis supported the hypothesis that ERAP1 may present an important susceptibility gene for AS. In addition, the results revealed that two functional SNPs (rs30187 and rs17482078) demonstrated the potential to decrease the enzymatic activity of ERAP1 by affecting its protein structure. Further protein structure-guided studies of the specificity and activity of these ERAP1 variants are therefore warranted.
| S-EPMC5865822 | biostudies-literature
Project description:Ankylosing spondylitis (AS) is an autoimmune disease that mainly affects the spinal joints, sacroiliac joints, and adjacent soft tissues. We conducted bioinformatics analysis to explore the molecular mechanism related to AS pathogenesis and uncover novel potential molecular targets for the treatment of AS. The profiles of GSE25101, containing gene expression data extracted from the blood of 16 AS patients and 16 matched controls, were acquired from the Gene Expression Omnibus (GEO) database. The background correction and standardization were carried out utilizing the transcript per million (TPM) method. After analysis of AS patients and the normal groups, we identified 199 differentially expressed genes (DEGs) with upregulation and 121 DEGs with downregulation by the limma R package. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis revealed that the DEGs with upregulation were mainly associated with spliceosome, ribosome, RNA-catabolic process, electron transport chain, etc. And the DEGs with downregulation primarily participated in T cell-associated pathways and processes. After analysis of the protein-protein interaction (PPI) network, our data revealed that the hub genes, comprising MRPL13, MRPL22, LSM3, COX7A2, COX7C, EP300, PTPRC, and CD4, could be the treatment targets in AS. Our data furnish new hints to uncover the features of AS and explore more promising treatment targets towards AS.
| S-EPMC8321739 | biostudies-literature
Project description:Recent studies have reported that circular RNAs (circRNAs) play a crucial regulatory role in a variety of human diseases. However, the roles of circRNAs in ankylosing spondylitis (AS) remain unclear. In this study, we conducted circRNA expression profiling of the spinal ligament tissues of patients with AS by RNA sequencing (RNA-seq) and analyzed the potential functions of differentially expressed circRNA by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to investigate the potential mechanisms associated with AS. The results showed that a total of 1,172 circRNAs were detected in the spinal ligament tissue samples, of which 123 circRNAs were significantly differentially expressed by a fold change ≥ 1.5 and p value < 0.05. Among these, 57 circRNAs were upregulated, and 66 were downregulated. GO and KEGG analyses demonstrated that the differentially expressed circRNAs were mainly involved in the regulation of biological processes of peptidyl-serine phosphorylation and human immune system that may be related to AS. In addition, the circRNA/miRNA interaction networks were established to predict the potential roles of differentially expressed circRNAs by bioinformatics analysis. Taken together, these results revealed the expression profiles of circRNAs and the potential functions of the differentially expressed circRNAs in the spinal ligament tissue of patients with AS, which may provide new clues for understanding the mechanisms associated with AS, and proceed to identify novel potential molecular targets for the diagnoses and treatment of AS.
| S-EPMC7313148 | biostudies-literature