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[目的]探讨miR-99a靶向卷曲蛋白(FZD5/FZD8)抑制角质形成细胞增殖的分子机制.[方法]应用QPCR和WB技术检测临床组织及各组细胞中miR-99a、FZD5/FZD8、β-catenin和CyclinD1的表达水平;MTT及BrdU实验检测细胞的增殖能力;双荧光素酶实验验证miR-99a的靶基因.[结果]miR-99a在银屑病皮损组织中显著低表达;过表达miR-99a可下调FZD5/FZD8、β-catenin和CyclinD1,抑制细胞增殖,抑制miR-99a可上调FZD5/FZD8、β-catenin和CyclinD1,并促进细胞的增殖;miR-99a可靶向调控FZD5和FZD8,过表达FZD5/FZD8可回复miR-99a对β-catenin和CyclinD1蛋白表达水平的抑制;miR-99a与FZD5/FZD8表达呈负相关.[结论]miR-99a可以靶向下调FZD5/FZD8的表达,并通过β-catenin和CyclinD1途径抑制角质形成细胞增殖.“,”[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.