Abstract
Epigenetic factors are heritable and ultimately play a role in modulating gene expression and, thus, in regulating cell functions. Non-coding RNAs have growing recognition as novel biomarkers and crucial regulators of pathological conditions in humans. Their characteristic feature is being transcribed in a tissue-specific pattern. Now, there is emerging evidence that lncRNAs have been identified to be involved in the differentiation of human skin, wound healing, fibrosis, inflammation, and immunological response. Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by fibrosis, vascular abnormalities, and immune system activation. The pathogenesis remains elusive, but clinical manifestations reveal autoimmunity with the presence of specific autoantibodies, activation of innate and adaptive immunity, vascular changes, and active deposition of extracellular matrix components leading to fibrosis. The use of multi-omics studies, including NGS, RNA-seq, or GWAS, has proposed that the non-coding genome may be a significant player in its pathogenesis. Moreover, it may unravel new therapeutic targets in the future. The aim of this review is to show the pathogenic role of long non-coding RNAs in systemic sclerosis. Investigation of these transcripts’ functions has the potential to elucidate the molecular pathology of SSc and provide new opportunities for drug-targeted therapy for this disorder.
Highlights
Several experimental studies revealed that specific gene sets are expressed in the peripheral blood and skin of Systemic sclerosis (SSc) patients [23,24,25,26], which are associated with fibrosis-related pathways such as transforming growth factor-β (TGF-β) and Wnt/β-catenin signaling pathways and collagen synthesis (COL4A3, COL4A4, COL5A2, COL13A1, COL22A1, CTGF) [27], immunologic response, B-cell signaling (BANK1), interleukin signaling (IL12A, IL12RB1, IRAK1), IFN signaling (IRF4, IRF5, STAT4), activated macrophages, chemokines, as well as keratin-related pathways [12,16,23,27,28,29,30,31]
Increased levels of circRNAs in human body fluids can be used as biomarkers of various diseases, including cancer [75,81]. piwi-interacting RNAs (piRNAs) are 26–32-nucleotides-long ncRNAs that play a crucial role in development, epigenetic regulation, and transposon silencing [75,82]. piRNAs are regulators of gene expression primarily present in germ cells, and demonstrate a strong tendency for uridine (U) at the 50 end [75]
This study revealed that OTUD6B-AS1 leads to reduced proliferation, suppressed apoptosis, and increased cyclin D1 expression
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Several experimental studies revealed that specific gene sets are expressed in the peripheral blood and skin of SSc patients [23,24,25,26], which are associated with fibrosis-related pathways such as TGF-β and Wnt/β-catenin signaling pathways and collagen synthesis (COL4A3, COL4A4, COL5A2, COL13A1, COL22A1, CTGF) [27], immunologic response, B-cell signaling (BANK1), interleukin signaling (IL12A, IL12RB1, IRAK1), IFN signaling (IRF4, IRF5, STAT4), activated macrophages, chemokines, as well as keratin-related pathways (keratin genes) [12,16,23,27,28,29,30,31]. We highlighted the biological role of lncRNAs and examined their function in the pathogenesis and development of immune-related diseases, in systemic sclerosis. We discussed their potential role as biomarkers and therapeutic agents
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