The eminent roles of ncRNAs in the pathogenesis of psoriasis

Abstract

Psoriasis is a chronic immune-related disorder in which both genetic and environmental parameters are involved. Recent studies have demonstrated dysregulation of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the peripheral blood or skin lesions of patients with psoriasis. While a number of lncRNAs such as MEG3, AL162231.4 and NONHSAT044111 have been down-regulated in the course of psoriasis, others including PRINS, MIR31HG, RP6‐65G23.1, MSX2P1, SLC6A14-1:1, NR_003062 have been up-regulated. Moreover, expressions of several miRNAs have been dysregulated in this disorder. Among dysregulated miRNAs are miR-126, miR-143, miR-19a and miR-155 whose diagnostic roles in the psoriasis have also been assessed. Dysregulated non-coding RNAs in this disorder participate in the regulation of chemokine signaling pathway and immune response, control of epidermal development and skin barrier as well as modulation of function of certain subsets of T cells. Besides, these transcripts possibly regulate activity of NF-κΒ, mTOR, MAPK and JAK-STAT signaling pathways. Besides, expression levels of circRNAs have been decreased in the psoriasis lesions. Massive alterations in the levels of lncRNAs and miRNAs in the psoriasis lesions or peripheral blood of affected individuals show participation of these transcripts in the pathogenesis of this disorder.

MicroRNA‐146a and microRNA‐146b deficiency correlates with exacerbated disease activity, and their longitude increment relates to etanercept response in psoriasis patients

“…Besides, miR‐146a was positively correlated with miR‐146b in psoriasis patients and disease controls, while the correlation of miR‐146a and miR‐146b displayed a positive trend in health controls. These results could be explained by that: miR‐146b probably functioned coordinately and assisted miR‐146a in the regulation of keratinocyte proliferation and inflammatory responses in psoriasis; hence, miR‐146a was positively correlated with miR‐146b in psoriasis patients and disease controls 20,21 …”

“…These data indicated that miR‐146a and miR‐146b were related to less exacerbated disease activity in psoriasis patients. Herein, several possible reasons were suggested: (a) MiR‐146a and miR‐146b probably suppressed the immune and inflammatory response, which mediated less release of cytokines and chemokines, resulting in less severe inflammation and decreased disease activity in psoriasis patients 1,13,14 ; (b) MiR‐146a and miR‐146b probably intercepted the proliferation and migration of keratinocytes but induced the apoptosis of keratinocytes in the lesioned skin, which devoted to the reduced disease activity in psoriasis patients, hence, miR‐146a and miR‐146b were correlated with less exacerbated disease activity in psoriasis patients 1,20,21 …”

“…These results could be explained by that: miR‐146b probably functioned coordinately and assisted miR‐146a in the regulation of keratinocyte proliferation and inflammatory responses in psoriasis; hence, miR‐146a was positively correlated with miR‐146b in psoriasis patients and disease controls. 20 , 21 …”

Recent update on immunopathogenesis of psoriasis

“…double-stranded or long noncoding RNA) generated through deregulated processing pathways along with their associated binding proteins (RNA sensors) are emerging as an important component of inflammation-related immune response pathways involving disease-associated molecular pattern sensing. [ 170 171 172 173 174 175 ] The paradigm shift in RNA metabolism-associated interactome is beginning to unravel the novel RBPs and splicing factors in context of psoriatic inflammatory pathways.…”

Maximizing the Utility of Transcriptomics Data in Inflammatory Skin Diseases

“…With the widespread applications of next-generation sequencing (NGS) technologies, huge numerous of human lncRNAs have been identified, producing a plenty of lncRNA resources in different contexts, such as LNCipedia (149) and NONCODE (150). Recently, an enrichment of dysregulated lncRNAs of typical inflammatory skin diseases has been reported (151). These dysregulated lncRNAs were mainly involved in epidermal differentiation, apoptosis and immune responses pathways (134,140,152).…”