MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that play important roles in the regulation of gene expression. We previously identified a characteristic miRNA expression profile in psoriasis, distinct from that of healthy skin. One of the most downregulated miRNAs in psoriasis skin was microRNA-125b (miR-125b). In this study, we aimed to identify the potential role(s) of miR-125b in psoriasis pathogenesis. In situ hybridization results showed that the major cell type responsible for decreased miR-125b levels in psoriasis lesions was the keratinocyte. Overexpression of miR-125b in primary human keratinocytes suppressed proliferation and induced the expression of several known differentiation markers. Conversely, inhibition of endogenous miR-125b promoted cell proliferation and delayed differentiation. Fibroblast growth factor receptor 2 (FGFR2) was identified as one of the direct targets for suppression by miR-125b by luciferase reporter assay. The expression of miR-125b and FGFR2 was inversely correlated in both transfected keratinocytes and in psoriatic skin. Knocking down FGFR2 expression by siRNA suppressed keratinocyte proliferation, but did not enhance differentiation. Altogether, our results demonstrate a role for miR-125b in the regulation of keratinocyte proliferation and differentiation, partially through the regulation of FGFR2. Loss of miR-125b in psoriasis skin may contribute to hyperproliferation and aberrant differentiation of keratinocytes.
: MicroRNAs are short non‐coding RNAs that regulate gene expression. Previously, in a genome‐wide screen, we found deregulation of microRNA expression in psoriasis skin. MicroRNA‐21 (miR‐21) is one of the microRNAs significantly up‐regulated in psoriasis skin lesions. To identify the cell type responsible for the increased miR‐21 level, we compared expression of miR‐21 in epidermal cells and dermal T cells between psoriasis and healthy skin and found elevated levels of miR‐21 in psoriasis in both cell types. In cultured T cells, expression of miR‐21 increased markedly upon activation. To explore the function of miR‐21 in primary human T helper cells, we inhibited miR‐21 using a tiny seed‐targeting LNA‐anti‐miR. Specific inhibition of miR‐21 increased the apoptosis rate of activated T cells. Our results suggest that miR‐21 suppresses apoptosis in activated T cells, and thus, overexpression of miR‐21 may contribute to T cell–derived psoriatic skin inflammation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.