Abstract：【Objective】The present study is aimed to investigate the molecular mechanism of miR-99a targeting FZD5/FZD8 to inhibit the proliferation of keratinocytes in psoriasis. 【Methods】The expression levels of miR-99a, FZD5/FZD8, β-catenin and CyclinD1 in tissues and cell lines were detected by QPCR and Western Blot. The proliferation of keratinocytes was detected by MTT and BrdU assays. The target gene of miR-99a was verified by dual luciferase reporter gene assay. 【Results】The expression of miR-99a was significantly down-regulated in psoriatic lesions. Overexpressed miR-99a downregulated the expression of FZD5/FZD8, β-catenin and CyclinD1, and inhibited keratinocyte proliferation as well. On the other hand, the inhibition of miR-99a showed upregulated FZD5/FZD8, β-catenin and CyclinD1 expression, while keratinocyte proliferation got enhanced. It was found that miR-99a targeted the regulation of FZD5 and FZD8. Overexpression of FZD5/FZD8 restored the inhibitory effect of miR-99a on β-catenin and CyclinD1 proteins. The expression of miR-99a and FZD5/FZD8 was inversely correlated. 【Conclusion】 MiR-99 can target FZD5/FZD8 gene to down-regulate their expression and inhibit keratinocyte proliferation through β-catenin/CyclinD1 signaling.
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2017, Vol. 34 
