Construction of competing endogenous RNA networks in systemic lupus erythematosus by integrated analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE266651 | GEO | 2024/05/10
REPOSITORIES: GEO
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Project description:The expression profiles of circRNAs in Jurkats cells, co-cultured with and without ionomycin, were analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca2+ influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNAs was investigated using transfection and RNA pull-down assay. After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca2+ influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biologic activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, enhanced IL-2 secretion and the protein expression of NFAT1.
2024-11-06 | GSE278650 | GEO
Project description:Purpose: Emerging evidence highlights the multifunctional role of noncoding RNAs (ncRNAs) in gastric cancer (GC) chemoresistance. However, the comprehensive expression profile and competing endogenous RNAs (ceRNAs) regulatory network of GC chemoresistance remain unanswered. Methods: The whole-transcriptome sequencing (RNA sequencing) was performed to comprehensively analyze the differentially expressed (DE) lncRNAs, miRNAs and mRNAs in cisplatin-resistant cells MGC-803/DDP and GC cells MGC-803. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions implicated with the DEncRNAs. Then, the cisplatin-resistant-related ceRNA network and potential regulatory axes were constructed by bioinformatic analysis. Results: We successfully generated cisplatin-resistant GC cell line MGC-803/DDP. Differential expression analysis showed that a total of 1,936 DElncRNAs, 2,194 DEmRNAs and 174 DEmiRNAs were identified. Functional enrichment analysis indicated that those DEncRNAs were mainly involved in neuroactive ligand-receptor interaction, drug metabolism and Hippo signaling pathway. Subsequently, the cisplatin-resistant-related ceRNA network was constructed with the widely accepted vital chemo-resistant-related genes and signaling pathways. In addition, two constructed regulatory axes (include FAM66C/miR-129-5p/7 mRNAs and SFTA1P/miR-206/FN1 or NRP1) were successfully validated by the Genomic Data Commons (GDC) GC data. Conclusion: The novel ceRNA network and the potential regulatory axes may provide the most comprehensive view of GC chemoresistance to date. Our findings uncovered potential biomarkers for prognostic prediction and novel therapeutic targets for reversing cisplatin resistance in GC.
2021-12-29 | GSE192631 | GEO
Project description:Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the most common cause of acute respiratory deterioration and death in IPF patients, with an elusive etiology and pathogenesis. Roles of noncoding RNAs in AE-IPF have been proposed, however, it was rare to find studies have systematically investigated the crosstalk among various transcripts until now. The construction of RNA functional networks such as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interaction networks could therefore facilitate our understanding of RNA interactions in AE-IPF. The study aimed to identify the expression differences of RNA transcripts in RNA sequencing from AE-IPF patients and stable IPF (S-IPF), and further to construct the potential RNA networks. Methods: Five AE-IPF patients and five S-IPF were recruited in this study to perform RNA sequencing and miRNA sequencing. The differentially expression profiles of lncRNAs, circRNAs, miRNAs and mRNAs between AE-IPF and S-IPF patients were identified for further analyses. Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of were performed. The competing endogenous RNAs (ceRNAs) network of lncRNA/circRNA-miRNA-mRNA was constructed, and the core regulatory molecules in the ceRNA network were analyzed. Results: A total of 69 lncRNAs, 150 circRNAs, 27 miRNAs and 56 mRNAs were differentially expressed between AE-IPF and S-IPF. GO and KEGG analysis show that differentially expression mRNAs are significantly associated with tight junction and Hepatitis C, etc. In the ceRNA network, all nodes are directly or indirectly involved in the progression of AE-IPF. 1 lncRNAs, 6 circRNAs, 1 miRNAs, and 5 mRNAs constituted a hsa-miR-150-5p core sub-network. Based on the analysis of ceRNA sub-network, NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 were considered to be the key ceRNA axis. Conclusions: In conclusion, this study reveals NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 may be the key ceRNA axis in the regulation of AE-IPF, providing clues for future studies on their roles for AE-IPF. Our findings will help to explore the pathological mechanism of AE-IPF from a transcriptomic perspective and provide enlightenment for the biomarker and therapeutic targets of AE-IPF.
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Project description:Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the most common cause of acute respiratory deterioration and death in IPF patients, with an elusive etiology and pathogenesis. Roles of noncoding RNAs in AE-IPF have been proposed, however, it was rare to find studies have systematically investigated the crosstalk among various transcripts until now. The construction of RNA functional networks such as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interaction networks could therefore facilitate our understanding of RNA interactions in AE-IPF. The study aimed to identify the expression differences of RNA transcripts in RNA sequencing from AE-IPF patients and stable IPF (S-IPF), and further to construct the potential RNA networks. Methods: Five AE-IPF patients and five S-IPF were recruited in this study to perform RNA sequencing and miRNA sequencing. The differentially expression profiles of lncRNAs, circRNAs, miRNAs and mRNAs between AE-IPF and S-IPF patients were identified for further analyses. Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of were performed. The competing endogenous RNAs (ceRNAs) network of lncRNA/circRNA-miRNA-mRNA was constructed, and the core regulatory molecules in the ceRNA network were analyzed. Results: A total of 69 lncRNAs, 150 circRNAs, 27 miRNAs and 56 mRNAs were differentially expressed between AE-IPF and S-IPF. GO and KEGG analysis show that differentially expression mRNAs are significantly associated with tight junction and Hepatitis C, etc. In the ceRNA network, all nodes are directly or indirectly involved in the progression of AE-IPF. 1 lncRNAs, 6 circRNAs, 1 miRNAs, and 5 mRNAs constituted a hsa-miR-150-5p core sub-network. Based on the analysis of ceRNA sub-network, NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 were considered to be the key ceRNA axis. Conclusions: In conclusion, this study reveals NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 may be the key ceRNA axis in the regulation of AE-IPF, providing clues for future studies on their roles for AE-IPF. Our findings will help to explore the pathological mechanism of AE-IPF from a transcriptomic perspective and provide enlightenment for the biomarker and therapeutic targets of AE-IPF.
2023-12-31 | GSE221937 | GEO
Project description:SLE patients are always with various disease manifestation. Various cytokines are pointed interacting and playing pathological roles in SLE although the etiopathology is still obscure. In this study, we aimed to investigate the effects of cytokine interactions in the immune response of SLE patients. Overexpressed interferon-inducible(IFI) genes were confirmed in peripheral blood from SLE patients. Using network-based analysis on the immune response-related genes, several networks including cytokines such as TNF and IFN-γ, or beta-estradiol(E2), were constructed. TNF-regulated genes were dominant in these networks but in vitro TNF stimulation on PBMCs showed no different responses in the expressions of these genes between SLE and healthy individuals. Co-stimulating experiments by TNF, IFN-γ, and E2 with IFN-α, revealed that TNF has repressive while IFN-γ essentially has synergistic effect with IFN-α on IFI gene expressions in vitro. E2 showed different effects on IFI gene expressions among 3 individuals. Peripheral blood was obtained from patients with SLE (n=11) and healthy women (n=6). Gene expression profile was analyzed using DNA microarray covering 30,000 human genes. Differentially expressed immune response-related genes were selected and analyzed by using Expression Analysis Systemic Explorer (EASE) based on Gene Ontology (GO) followed by network pathway analysis with Ingenuity Pathways Analysis (IPA).
2009-05-31 | E-GEOD-12374 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
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