Role of an imbalanced miRNAs axis in pathogenesis of psoriasis: novel perspectives based on review of the literature

Abstract

BACKGROUNDSpecific profile of microRNAs (miRNAs, miR) expressed in psoriasis has been identified in the past few years, while the studies on roles and molecular mechanisms of these miRNAs are still on the way. In our previous study, four specific miRNAs (miR-31, miR-203, hsa-miR-99a and miR-125b) were found to be specifically altered in psoriatic lesions.We therefore conducted a systematic literature review in this study to reveal the role of these miRNAs in the pathogenesis of psoriasis in order to inform future research.METHODSThe related articles indexed in PubMed (MEDLINE) database were searched and analyzed. We identified eligible studies related to the mechanism research of miR-31, miR-203, hsa-miR-99a and miR-125b in psoriasis or psoriatic lesional skin from inception up to July 2016. The experts in the field of miRNAs and Psoriasis were involved in analysis process.RESULTBoth miR-31 and miR-203 are dramatically upregulated in psoriatic lesions. The former plays the pro-proliferative, pro-differentiative and pro-inflammatory roles and the latter holds the potentials for anti-proliferation, pro-inflammation and pro-differentiation in psoriatic keratinocytes. Conversely, both hsa-miR-99a and miR-125b are significantly downregulated in psoriatic skin. These two miRNAs are able to inhibit proliferation while promote differentiation of psoriatic keratinocytes, and miR-125b can also suppress inflammation in psoriatic lesions. By analyzing the contexts related to these miRNAs, we found that each of them does not act alone but rather work in concert with other miRNAs. The imbalance between miR-31/miR-203and hsa-miR-99a/miR-125b may contribute to the intense proliferation and abnormal differentiation of psoriatic keratinocytes, which is a characteristic of pathogenesis of psoriasis.CONCLUSIONAn imbalanced miRNAs axis was for the first time outlined. Apparently, upregulation of miR-31/miR-203 and downregulation of hsa-miR-99a/miR-125b work together in concert to facilitate the development of psoriasis pathogenesis. Further work in this field holds the potentials to open a new way to study psoriasis.

Dendritic cell recruitment and activation in autoimmunity

“…Indeed, this was recently demonstrated both in an experimental tumor microenvironment and in a model of neuronal damage [157,158]. miRNA expression is dysregulated in many diseases, including SLE and psoriasis [159,160]. It is therefore possible that miRNAs released by diseased tissues may concur for pDCs activation also in autoimmune contexts.…”

Association between histopathological changes and expression of selected microRNAs in skin of adult patients with IgA vasculitis

“…30 Our results therefore suggest that miR-203-3p might also be involved in these processes in IgAV. In addition, the altered expression of miR-203 found in psoriasis 31 and rheumatoid arthritis 32 suggests its involvement in immune-mediated diseases.…”

Levels of miR‐31 and its target genes in dermal mesenchymal cells of patients with psoriasis

“…In our study, because of the low levels of miR‐31 in patients with psoriasis, the expression level of EIG121L was higher in DMSCs from patients with psoriasis than in control DMSCs. Increased epidermal differentiation could result in the imbalance between the proliferation and differentiation of KCs, which could give rise to the pathological changes observed in psoriasis …”

“…Recently, there has been increasing attention on the role of miR‐31 in the development of psoriasis. Some studies have reported that miR‐31 is overexpressed in proliferating KCs in lesions of patients with psoriasis . miR‐31 regulates a variety of cellular processes, such as cell proliferation, differentiation, and apoptosis, and its expression is deregulated in autoimmune disorders such as psoriasis …”