BackgroundPsoriasis is a complex disease at the cellular, genomic and genetic levels. The role of microRNAs in skin development was shown in a keratinocyte-specific Dicer knockout mouse model. Considering that two main characteristics of psoriasis are keratinocytes hyperproliferation and abnormal skin differentiation, we hypothesized that aberrant microRNA expression contributes to the psoriatic phenotype. Here, we describe the differential expression of miRNAs in psoriatic involved and uninvolved skin as compared to normal skin, revealing an additional aspect of this complex disorder.Methodology/Principal FindingsExpression arrays were used to compare microRNA expression in normal skin versus psoriatic involved and uninvolved skin. Fourteen differentially expressed microRNAs were identified, including hsa-miR-99a, hsa-miR-150, hsa-miR-423 and hsa-miR-197. The expression of these microRNAs was reevaluated by qPCR. IGF-1R, which is involved in skin development and the pathogenesis of psoriasis, is a predicted target of hsa-miR-99a. In an in situ hybridization assay, we found that IGF-1R and miR-99a are reciprocally expressed in the epidermis. Using a reporter assay, we found that IGF-1R is targeted by hsa-miR-99a. Moreover, over expression of miR-99a in primary keratinocytes down-regulates the expression of the endogenous IGF-1R protein. Over expression of miR-99a also inhibits keratinocyte proliferation and increases Keratin 10 expression. These findings suggest that overexpression of hsa-miR-99a in keratinocytes drives them towards differentiation. In primary keratinocytes grown in high Ca++, miR-99a expression increases over time. Finally, we found that IGF1 increases the expression of miR-99a.Conclusions/SignificanceWe identified several microRNAs that are expressed differentially in normal and psoriatic skin. One of these miRNAs is miR-99a that regulates the expression of IGF-1R. Moreover, miR-99a seems to play a role in the differentiation of keratinocytes. We suggest that miR-99a is one of the regulators of the IGF-1R signaling pathway in keratinocytes. Activation of IGF1 signaling results in elevation of miR-99a which represses the expression of IGF-1R.

UVB is a safe and efficient treatment option for generalized cutaneous lichen planus.

The nucleolar organizer regions (NORs) are chromosomal loops of DNA and proteins involved in ribosomal synthesis. By silver staining, they can be identified as black dots (AgNORs) in the nuclei. Their size and number reflect cell and nuclear activity. Therefore, AgNOR count may correlate with the proliferative activity of tumors. In malignant melanoma, correlation between AgNOR count and the growth phase was found. However, the value of AgNORs in determining prognosis is disputable. Our purpose was to evaluate the role of AgNORs in predicting the biological behavior of melanoma. Paraffin-embedded sections of 30 cases of primary melanoma, 0.4-5 mm thick (mean, 1.6 mm) were stained with silver. Follow-up of all patients was at least 5 years. For each tumor, at least 50 cells were randomly selected for AgNOR count at a final magnification of 500, and the mean of AgNOR content was calculated. Sample parameters corresponded well to the epidemiology and the natural history of melanoma. AgNOR counts (0.78-4.26; mean, 1.42+/-0.72) correlated with tumor thickness (p = 0.01); thus, most superficial tumors had low AgNOR counts, whereas most deep tumors (> or = 1.5 mm) showed high counts. Patients who had tumors with AgNOR counts lower than the median had longer disease-free interval (DFI) than did patients who had tumors with higher counts (p = 0.02). Furthermore, in a multivariate Cox analysis, AgNOR count was independent of tumor thickness in determining DFI (p = 0.05). Therefore, AgNORs may serve as a parameter to predict more accurately the progression of melanomas (mainly thin ones). Larger studies are needed in order to consolidate these preliminary results and to characterize AgNOR value further as a prognostic factor in melanoma.