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    Integrated system biology investigation (in-silico) of Co-expression of the lncRNAs and mRNAs associated with the immune system in Lupus (SLE)

  • Parisa Rabiei Chamgordani,1 Mahdieh Bakhshayesh,2 Mansoureh Azadeh,3,*
    1. Zist Fanavari Novin Biotechnology Institute
    2. Zist Fanavari Novin Biotechnology Institute
    3. Zist Fanavari Novin Biotechnology Institute


  • Introduction: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterized by overactive inflammation and aberrant activation of lymphocytes. (1) miRNAs, discovered non-coding RNAs, regulate gene expression at the post-transcriptional level by base pairing with 3’UTR of their targeted mRNAs annotated as to their targetome. Moreover, C-X-C motif chemokine 10 (CXCL10) was significantly elevated in a systemic lupus erythematosus (SLE) cohort compared to healthy donors. STAT1, CCL2, and CXCL10 are potentially useful indicators of therapeutic action in SLE patients. CXCL10 was correlated with type-I IFN in high STAT1 patients similar to that in untreated patients. (2) Analyzing the expression mRNAs microarray from childhood-onset lupus (cSLE) skin lesion tissues and normal skin with GSE148810. (3)
  • Methods: miRNAs were regained from miRwalk and Enrichr databases, followed by examining their expression in childhood-onset lupus (cSLE) skin lesion tissues using GEO and DAVID database. Interaction lncRNAs and mRNAs by Enrichr databases and lncHUB databases. The miRWalk was used to analyze miRNA–mRNA interactions. The Pathway enrichment analysis was carried out using the online databases KEGG and Reactome. The expression of lncRNAs in different tissues has been examined by the lnCAR databases. comparing the expression of genes in different tissue by Gepia2 databases and The protein-protein interaction analysis by STRING online software.
  • Results: We found that CXCL10, CXCL11, CXCL9, and IRF1 mRNAs had the most significant expression changes (adj.P.Val<0.05). We have examined interactions between lncRNAs and mRNAs. The expression of mRNAs including CXCL10 and CXCL9 have miR-1278 and CXCL9 and CXCL11 have miR-379. Furthermore, CXCL9, CXCL10, and CXCL11 have similar microRNAs including mmu-miR-590-5p and mmu-miR-21. We found LncRNAs including Linc02195, PSMB8-AS1, and Linc02446 that are common in CXCL9, CXCL10, CXCL11, and IRF1. The existence of CXCL9, CXCL10, CXCL11, and IRF1 had CeRNA with lncRNAs, which indicates the existence of a complex network that can be used in gene therapy or drug. Also, we have a high expression of PSMB8-AS1 in gastric cancer. Also, we have a high expression of PSMB8-AS1 in gastric cancer. There are common pathways between CXCL9, CXCL10, and CXCL11 including Toll-like receptor signaling, Cytokine-cytokine receptor interaction, and chemokine signaling pathway. Additionally, CXCL10 is involved in TNF signaling pathway. The TNF signaling pathway plays an important role in various physiological and pathological processes, including cell proliferation, differentiation, apoptosis, modulation of immune responses, and induction of inflammation. CXCL10 is a potentially useful indicator of therapeutic action in SLE patients.
  • Conclusion: We identified several hub lncRNA-mRNA networks involved in regulating various biological processes in systemic lupus erythematosus (SLE). CXCL9, CXCL10, CXCL11, IRF1, and also, Co-Expression LINC0219, LINC02446, PSMB8_AS1 could be prognostic biomarkers in the Immune system. Moreover, LINC0219, LINC02446, PSMB8_AS1 play a role in the Cytokine-cytokine receptor interaction pathway.
  • Keywords: cSLE, IRF1, CXCL10, PSMB8-AS1, Network complex, TNF signaling pathway