Long Non-Coding RNAs Modulate Sjögren’s Syndrome Associated Gene Expression and Are Involved in the Pathogenesis of the Disease

Abstract

Primary Sjögren’s syndrome (pSjS) is a chronic systemic autoimmune disorder, primarily affecting exocrine glands; its pathogenesis is still unclear. Long non-coding RNAs (lncRNAs) are thought to play a role in the pathogenesis of autoimmune diseases and a comprehensive analysis of lncRNAs expression in pSjS is still lacking. To this aim, the expression of more than 540,000 human transcripts, including those ascribed to more than 50,000 lncRNAs is profiled at the same time, in a cohort of 16 peripheral blood mononuclear cells PBMCs samples (eight pSjS and eight healthy subjects). A complex network analysis is carried out on the global set of molecular interactions among modulated genes and lncRNAs, leading to the identification of reliable lncRNA-miRNA-gene functional interactions. Taking this approach, a few lncRNAs are identified as targeting highly connected genes in the pSjS transcriptome, since they have a major impact on gene modulation in the disease. Such genes are involved in biological processes and molecular pathways crucial in the pathogenesis of pSjS, including immune response, B cell development and function, inflammation, apoptosis, type I and gamma interferon, epithelial cell adhesion and polarization. The identification of deregulated lncRNAs that modulate genes involved in the typical features of the disease provides insight in disease pathogenesis and opens avenues for the design of novel therapeutic strategies.

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

“…The expression analysis of lncRNAs in SS patients has shown lncRNAs LINC00657, LINC00511 and CTD-2020K17.1 potentially associated with the disease. These 3 lncRNAs target different genes involved in B cell physiology and malignancy, including IL15, WDR5, GNAI2, LTßR, CBX8, BAK1, BAX ext [ 60 ]. IL15 and WDR5 play an important role in B cell proliferation and differentiation; GNAI2 regulates B cell trafficking to the lymph nodes [ 61 ]; LTßR and CBX8 are involved in GC formation in inflamed tissues [ 62 , 63 ], and BAK1 and BAX are overexpressed in B cell lymphoma [ 64 ].…”

Management of Sjögren's Syndrome: Present Issues and Future Perspectives

“…Epigenetic studies on the regulatory role of microRNAs and long non-coding RNAs have revealed that specific probes are significantly overexpressed in patients with pSS, and that they could assume a diagnostic role in this disorder in the near future (143)(144)(145). On the contrary, the level of other microRNAs has been found to be reduced in pSS patients with lymphoma or pre-lymphoma condition (146).…”

Involvement of long noncoding RNAs in the pathogenesis of autoimmune diseases

“…The transcriptome analysis of PBMCs from pSS patients and healthy controls identified 199 differentially expressed lncRNAs. Through a complex network analysis of lncRNA–miRNA–gene functional interactions, three lncRNAs, namely, LINC00657, LINC00511 and CTD-2020K17.1, were identified to be involved in the pathogenesis of pSS [ 126 ]. Recently, a study demonstrated that the lncRNA PVT1 is upregulated in the CD4 + T cells of SS patients.…”