Dissecting the Role of NF-κb Protein Family and Its Regulators in Rheumatoid Arthritis Using Weighted Gene Co-Expression Network.

摘要: Rheumatoid arthritis (RA) is a chronic synovial autoinflammatory disease that destructs the cartilage and bone, leading to disability. The functional regulation of major immunity-related pathways like nuclear factor kappa B (NF-κB), which involved in inflammatory reactions underlying development RA, remains be explored. Therefore, this study has adopted statistical knowledge-based systemic investigations (like gene correlation, semantic similarity, topological parameters based on graph theory) expression status NF-κB protein family (NKPF) its regulators tissues trace molecular through these contribute RA. A complex protein-protein interaction map (PPIM) 2,742 genes 37,032 interactions was constructed from differentially expressed (p ≤ 0.05). PPIM further decomposed into Regulator Allied Protein Interaction Network (RAPIN) between (5 NKPF, 31 seeds, 131 hubs, 652 bottlenecks). Pathway network analysis shown RA-specific disturbances connectivity seed (RIPK1, ATG7, TLR4, TNFRSF1A, KPNA1, CFLAR, SNW1, FOSB, PARVA, CX3CL1, TRPC6) NKPF members (RELA, RELB, NFKB2, REL). Interestingly, are known for their involvement inflammation immune system (signaling by interleukins, cytokine signaling system, NOD-like receptor signaling, MAPK Toll-like TNF signaling) connected This study, first time, reports along with other NK regulatory genes, plays an important role RA pathogenesis might act as potential biomarker Additionally, play roles pathogenesis, well facilitate effective targeted therapies. Our integrative data network-based methods could accelerate identification novel drug targets high-throughput genomic data.