Psoriasis is a complex inflammatory autoimmune skin illness that causes epidermal keratinocyte hyperproliferation and dedifferentiation. In a previous study we did in the lab, we found that treating human keratinocytes (HaCaT) with PUVA increased the expression of hsa-miR-718 compared to control. In this study, an imiquimod (IMQ)-induced mouse model and HaCaT were used to look at how overexpressing miR-718 could help treat psoriasis and its causes. To gain more understanding, the in vivo study used the JAK1/3 inhibitor tofacitinib. We observed that miR-718 overexpression leads to the inhibition of JAK-STAT signalling, as evidenced by the reduced expression of STAT1, JAK proteins, and their phosphorylated forms, both in vitro and in vivo. Luciferase assay demonstrated the direct inhibition of STAT1 due to miR-718 overexpression. Additionally, in vitro experiments showed downregulation of STAT2 and STAT3. Inhibition of basal miR-718 in HaCaT overactivates JAK-STAT signalling proteins. In psoriatic mice, ectopic miR-718 reduces NF-kB, a key mediator of inflammation. IHC shows lower acanthosis and parakeratosis in IMQ-induced psoriatic mice. In the skin of mice that had been miR-718 transfected, there was less VEGF, MMP7 and MMP9. Understanding how miR-718 improves psoriasis not only provides new information but also inspires hope for its potential use as a psoriasis treatment.
