MiR-99a inhibits keratinocyte proliferation by targeting Frizzled-5 (FZD5)/FZD8 through β-catenin signaling in psoriasis

Psoriasis, a common chronic skin disorder, is characterized by hyperproliferation and aberrant differentiation of keratinocytes and infiltration of inflammatory cells into the dermis and epidermis. MicroRNAs (miRNAs) are a large family of highly conserved small non-coding RNA which regulates diverse biological process, including cell proliferation, by modulating gene expression at the posttranscriptional level. In the present study, we indicated that miR-99a was specifically downregulated in psoriatic dermatic lesions, and could inhibit HaCaT cells' proliferation; by direct targeting, miR-99a could also regulate the expression of Frizzled-5 (FZD5)/Frizzled-8 (FZD8). In addition, we found that the downstream factor of FZD5/FZD8 signaling, beta-catenin, and the downstream target gene of beta-catenin, cyclinD1, could be suppressed by miR-99a; the suppressive effect of miR-99a on beta-catenin and cyclinD1 could be partially abolished by forced FZD5/FZD8 expression. Taken together, we assume that miR-99a inhibits HaCaT cells' proliferation by targeting FZD5/FZD8 through downstream factors beta-catenin and cyclinD1, and provide diagnostic markers and a novel target for psoriasis treatment.