Background/Aims: Wnt5a is overexpressed in psoriasis lesions, however the mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not clear. To address this, the expression of Wnt5a in psoriatic lesions and its effect on keratinocyte cell proliferation and apoptosis was examined in vitro. Methods: The expression levels of WNT5A, and genes encoding its receptors frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short interfering (si)RNAs was performed in cultured HaCaT keratinocytes and normal human keratinocytes (NHK), and the expression of Wnt5a, protein kinase C (PKC), and β-catenin were determined, and cell cycle activity, proliferation and apoptosis were assessed. Results: The expression of WNT5A, FZD2 and FZD5 mRNA and protein were increased in psoriatic lesions. Wnt5a knockdown suppressed proliferation and induced apoptosis in HaCaT and NHK cells. Additionally, expression of PCNA, MKI67, CCND1, BCL2, CTNNB1, and genes encoding PKC and survivin were downregulated, whereas CASP3 was upregulated. The mRNA levels of the Wnt pathway inhibitors DKK1 and SFRP1 were upregulated, Western blotting analyses demonstrated reduction in β-catenin and PKC protein levels. Conclusion: Knockdown of Wnt5a suppresses the proliferation of keratinocytes and induces apoptosis by inhibiting the Wnt/β-catenin or Wnt5a/Ca²⁺ pathways.

Previous research indicates that microRNA-25 (miR-25) regulates carcinogenesis and the progression of various cancers, but the role of miR-25 in melanoma remains unclear. We observed that miR-25 was significantly upregulated in melanoma cell lines and tissue samples. Downregulation of miR-25 markedly suppressed invasion and proliferation of melanoma cells in vitro; however, overexpression of miR-25 markedly increased melanoma cell invasion and proliferation. Moreover, we observed Dickkopf-related protein 3 (DKK3) as a direct target of miR-25 in vitro. Upregulation of DKK3 partially attenuated the oncogenic effect of miR-25 on melanoma cells. Ectopic expression of miR-25 in melanoma cells induced β-catenin accumulation in nuclear and inhibited TCF4 (T cell factor 4) activity, as well as the expression of c-Myc and Cyclin D1. In a nude xenograft model, miR-25 upregulation significantly increased A375 melanoma growth. In summary, miR-25 is upregulated in melanoma and promotes melanoma cell proliferation and invasion, partially by targeting DKK3. These results were indicated that miR-25 may serve as a potential target for the treatment of melanoma in the future.

Psoriasis is a chronic disease which carries the emotional and social burden, promotes joint disability and raises comorbidity possibility in patients. Obesity is closely correlated with the occurrence of psoriasis and adipokines produced by adipose tissues were found to be critical culprits. Chemerin is one of them and its expression was increased in patients with psoriatic arthritis. In our hypothesis, chemerin might act on keratinocytes and promote an inflammatory response, which plays an essential role in psoriatic epidermis. To validate our hypothesis, HaCaT cells and primary human keratinocytes were treated with chemerin (5, 10, and 20 ng/mL for 24 hours). Enzyme‐linked immunosorbent assay (ELISA) was used to determine the secretion of inflammatory factors. Nuclear factor‐κB (NF‐κB) activation and p65 acetylation were evaluated by Western blot analysis. The expression and activity of sirtuin 1 (sirt1), a deacetylase act on p65, were also analyzed. The results showed that chemerin prompted inflammatory factors secretion, NF‐κB activation and p65 acetylation through chemerin receptor 23 receptor. Chemerin constrained the expression and deacetylase activity of sirt1 through augment of reactive oxygen species (ROS) production. Additionally, chemerin exacerbated psoriasiform dermatitis in imiquimod‐treated mice model. In conclusion, chemerin can seduce inflammatory response and promote NF‐κB activation through inhibition of sirt1 activity by ROS production.

Alterations in the levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role and underlying mechanism of miR-4262 in the proliferation of human cutaneous malignant melanoma (CMM) cells. The expression levels of miR-4262 were significantly upregulated in cancerous tissues compared with those in matched adjacent normal tissues from 110 CMM patients. miR-4262 was also regulated in five types of CMM cell lines, displaying an opposite expression pattern to that of Kruppel-like 6 (KLF6), a proven tumor suppressor in several cancers other than CMM. KLF6 overexpression sharply reduced A375 cell proliferation, suppressed the activation of epidermal growth factor receptor (EGFR) and increased p21 expression levels, while knockdown of KLF6 by siRNA transfection had an opposite effect. Furthermore, KLF6 was proven to be a direct target gene of miR-4262 by bioinformatic analysis and KLF6‑3'UTR luciferase reporter assay. Finally, our data on miR-4262 mimic and inhibitor transfection indicated that miR-4262 could markedly reduce the expression of KLF6 protein and had a stimulatory effect on A375 cell proliferation. Our findings indicate that KLF6 acts as a tumor suppressor in CMM cells and miR-4262 promotes the proliferation of CMM cells through KLF6-mediated EGFR inactivation and p21 upregulation.

Vitiligo is a common depigmenting acquired disorder affecting about 1-2% of the world population, regardless of race, ethnic background, or gender. It is characterized by the appearance of milky white maculae because of a loss of melanocytes. The disfiguring nature of vitiligo causes high psychosocial morbidity. This is especially pronounced in populations with darker skin tone, likely because of the marked contrast. A variety of nonsurgical treatment regimens are currently employed in vitiligo. We reviewed the latest studies carried out on different nonsurgical treatment modalities used in vitiligo. All nonsurgical treatment aid to repigment or depigmentation the skin, however, many of them require a prolonged treatment course and may yield minimal results as well as carry unwanted side effects. There is a need for further research into the causes of vitiligo and into discovering better treatments.