Exploration of the molecular mechanisms, shared gene signatures, and MicroRNAs between systemic lupus erythematosus and diffuse large B cell lymphoma by bioinformatics analysis

Abstract

Background Systemic lupus erythematosus (SLE) is a complex heterogeneous systemic autoimmune disease. Previous studies have shown that SLE may be related to diffuse large B cell lymphoma (DLBCL), but the mechanism of their relationship is still unclear. The present study aimed to explore the common genetic molecular mechanisms, core shared genes, and miRNAs between SLE and DLBCL as well as to investigate the diagnostic markers of DLBCL. Methods The SLE and DLBCL microarray data were downloaded from the comprehensive Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules. Four core shared genes were screened out by various algorithms and validated in other cohorts. Finally, we constructed a common core gene-miRNA network using the human microRNA disease database (HMDD) and TarBase. Results Using WGCNA, four modules were identified as important modules for SLE and DLBCL. Enrichment analysis of the shared genes showed that the highly activated NF-κB pathway was a common feature of the pathophysiology. Four core shared genes, namely, PSMB10, PSMB4, TAF10, and NFΚBIA, were screened out. These core shared genes were significantly upregulated in both diseases, and they may be potential diagnostic markers of DLBCL. The core gene-miRNA network showed that miR-155–5p, regulating the shared NF-κB pathway, may play an important role in the susceptibility of SLE patients to DLBCL. Conclusion The present study revealed that NF-κB pathway in SLE may be a crucial susceptible factor for DLBCL. In addition, we identified PSMB10, PSMB4, TAF10, NFΚBIA and miR-155 involved in the common pathogenesis as potential biomarkers and therapeutic targets for DLBCL.

Participation of the TBP‐associated factors (TAFs) in cell differentiation

“…TAF10 is also part of the PCAF histone acetylase complex, the TATA‐binding protein‐free TAF complex (TFTC), and the STAGA transcription coactivator‐HAT complex (Martinez et al, 2001; Zhao et al, 2008). Moreover, TAF10 has been associated with human dilated cardiomyopathy (Li et al, 2018) and Systemic Lupus Erythematosus (Peng et al, 2022), among other diseases.…”

Role of estrogen receptor signaling pathway-related genes in diffuse large B-cell lymphoma and identification of key targets via integrated bioinformatics analysis and experimental validation

“…Although patient outcomes have improved by combining CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with the monoclonal anti-CD20 antibody rituximab ( 9 , 10 ), however, 30-40% of patients still develop drug resistance during treatment ( 11 – 15 ). The application of next-generation sequencing has revealed a significant degree of molecular and clinical heterogeneity in DLBCL ( 16 – 18 ). This heterogeneity presents a series of challenges to the understanding and treatment of DLBCL.…”