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Background The extensive involvement of microRNAs (miRNAs) in the pathogenesis of psoriasis is well documented. However, little is known about the contribution of specific miRNAs to the prevalence of this disease. Objectives To explore the role of miR-145-5p in psoriasis. Methods miRNA microarray analysis was performed in four patients with psoriasis and four controls. Quantitative reverse-transcriptase polymerase chain reaction and fluorescence in situ hybridization were used to identify the dysregulated miR-NAs. Luciferase assays were performed to determine whether miR-145-5p targets mixed-lineage kinase (MLK)3. CCK-8 assay and Magnetic Luminex Assay were performed to measure cell proliferation and chemokine secretion. Western blot analysis was used to investigate the protein levels of MLK3 and its downstream effectors. Mouse models of psoriasis were established for in vivo experiments.Results miR-145-5p was downregulated in psoriatic lesional skin. Luciferase assays showed that MLK3 is a direct target of miR-145-5p. Overexpression of miR-145-5p in normal human epidermal keratinocytes (NHEKs) suppressed cell proliferation and secretion of chemokines. In contrast, silencing miR-145-5p promoted NHEK proliferation and increased chemokine secretion. Silencing MLK3 abrogated miR-145-5p inhibitor-induced promotion of cell proliferation and chemokine expression. miR-145-5p regulates nuclear factor-jB and signal transducer and activator of transcription 3 by targeting MLK3. Delivery of agomiR-145-5p into the skin decreased epidermal hyperplasia and ameliorated psoriasis-like dermatitis. Delivery of antagomiR-145-5p led to the opposite effects. Conclusions Our findings indicate that miR-145-5p negatively regulates proliferation and chemokine secretion of NHEKs by targeting MLK3, and downregulation of miR-145-5p contributes to skin inflammation in psoriasis lesions. What's already known about this topic?• Psoriasis is a chronic, immune-mediated disease and has a strong genetic component.• Aberrant microRNA expression contributes to psoriasis development and progression.• miR-145-5p has been studied in immune-mediated disease, but not in psoriasis. What does this study add?• miR-145-5p plays important functions in psoriasis by targeting mixed-lineage kinase 3.• Downregulation of miR-145-5p promotes keratinocyte proliferation and exacerbates skin inflammation in psoriasis.

Background/Aims: Circular RNAs (circRNAs) are evolutionary conserved circular non-coding RNAs that play a role in several diseases by sequestering (sponging) microRNAs (miRNAs). However, their role in psoriasis remains unclear. In the present study, we investigated the expression of circRNAs and analyzed their potential functions in psoriasis. Methods: The SBC human ceRNA array V1.0 was used to analyze circRNA expression in psoriatic lesions and normal healthy skin tissues. Functional analyses were performed using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Putative miRNA response elements (MREs) were identified using miRNA target prediction software. Six upregulated circRNAs were verified by quantitative real-time reverse transcription polymerase chain reaction in psoriatic lesions and healthy skin tissues. Results: A total of 4956 circRNAs (3016 upregulated and 1940 downregulated; fold change ≥2 and p< 0.05) were identified as differentially expressed in psoriasis. Furthermore, 4405 MREs were identified among the differentially expressed circRNAs. hsa_circ_0061012 was upregulated in psoriatic lesions compared with normal healthy skin tissues. The top five MREs of hsa_circ_0061012 were hsa-miR-7157-5p, hsa-miR-4769-3p, hsa-miR-6817-5p, hsa-miR-4310, and hsa-miR-6882-3p. GO analysis was carried out to investigate the biological functions enriched among the upregulated targets of five miRNAs in psoriasis. The GO analysis identified that most of top 30 of GO enrichment are related to psoriasis. Conclusion: hsa_circ_0061012 might be a candidate biomarker for psoriasis. The results provide a new perspective for a better understanding of ceRNA-mediated gene regulation in psoriasis, and provide a novel theoretical basis for further studies on the function of circRNA in psoriasis.

Long noncoding RNAs (lncRNAs) serve important roles in the biology of autoimmune diseases and immune-associated disorders. To identify lncRNAs specifically associated with psoriasis, the expression of lncRNAs from biopsies obtained from patients with psoriasis were compared with samples obtained from healthy volunteers using a microarray. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of 10 identified dysregulated lncRNAs. Cis- and trans-regulated target genes of lncRNAs were predicted. The results of microarray analysis indicated that 2,194 lncRNAs and 1,725 mRNAs were significantly dysregulated. Gene Ontology and pathway analyses among the dysregulated genes were performed. Co-expression network analysis was also performed to study molecular interactions. Several identified pathways were associated with psoriasis. Among the 2,194 dysregulated lncRNAs, 1,549 of these had cis- or trans-regulated predicted target genes. Among the 1,725 dysregulated mRNAs, 289 of the cis-regulated target genes and 262 of the trans-regulated target genes may be regulated by the differentially expressed lncRNAs; 10 differentially expressed lncRNAs were randomly selected and then validated. Of these lncRNAs, 7 exhibited the same expression profile as determined via microarray analysis, of which 3 lncRNAs were upregulated and 4 lncRNAs were downregulated. To the best of our knowledge, the present study is the first in which a microarray has been used to investigate the expression profile of lncRNAs associated with psoriasis. Additionally, the expression levels of the 10 aforementioned lncRNAs associated with psoriasis were validated in the present study for the first time using RT-qPCR. The findings demonstrated that lncRNAs may contribute to the pathogenesis of psoriasis and suggested their potential diagnostic and therapeutic value. Furthermore, the findings of the present study suggest that the combined actions of several lncRNAs may contribute to the pathogenesis of psoriasis.

BackgroundExosomes are nanovesicles secreted from endosomal membranes. The immunomodulatory effect of mesenchymal stem cells (MSCs) is mediated by MSCs-derived exosomes (MSCs-exo). MSCs-exo are attractive candidates for use in cell therapy for several in ammatory diseases including psoriasis. We investigated whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-Exo) ameliorate psoriasis-like skin in ammation via the IL-23/IL-17 axis. MethodsHucMSCs-Exo were isolated by differential ultracentrifugation. Imiquimod (IMQ)-induced mice were subcutaneously injected with hucMSCs-Exo on days 0, 2 and 4. H&E staining and Western blotting were performed, and tissue histopathology and STAT3/p-STAT3, IL-17, IL-23, and CCL20 levels were assessed. HucMSCs-Exo were co-cultured with dendritic cells (DCs) and HaCat cells in vitro. Western blotting, ow cytometry and ELISAs were then performed to measure STAT3/p-STAT3, IL-17, IL-23, and CCL20 levels. Results Subcutaneous injection of hucMSCs-Exo signi cantly ameliorated symptoms and diminished the clinical and pathological scores of psoriasis in IMQ-induced mice. In MSCs-exo-treated mice, STAT3/p-STAT3, IL-17, IL-23 and CCL20 levels were decreased. HucMSCs-Exo co-cultured in vitro with DCs suppressed DC maturation and activation and inhibited IL-23 secretion. HucMSCs-Exo co-cultured with HaCat cells reduced STAT3/p-STAT3, IL-17, IL-23, and CCL20 levels. ConclusionsHucMSCs-Exo can effectively ameliorate psoriasis-like skin in ammation in mice via the IL-23/IL-17 axis. Furthermore, hucMSCs-Exo exhibit immunomodulatory potency by inhibiting the maturation and activation of DCs and blocking the positive feedback effect of IL-17 on keratinocytes. Our data offer a novel therapeutic approach for chronic in ammatory skin diseases such as psoriasis by leveraging the immunomodulatory effects of hucMSCs-Exo.