MicroRNA-194 regulates keratinocyte proliferation and differentiation by targeting Grainyhead-like 2 in psoriasis

详细信息    查看全文

• 作者：Xiaoyun Yu^a ; ^b ; Jingang An^c ; Yunhui Hua^b ; Zihai Li^b ; Ning Yan^b ; Weixin Fan^d ; ^{fanweixin_njmu@163.com} ; Chuan Su^a ; ^{chuansu_njmu@163.com}
• 关键词：BrdU ; bromodeoxyuridine ; CK1 ; cytokeratin 1 ; CK10 ; cytokeratin 10 ; GRHL2 ; Grainyhead like 2 ; IL ; interleukin ; miRNAs ; microRNAs ; MTT ; 3-(4 ; 5-dimethyl-thiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; RT-qPCR ; Real-time quantitative polymerase chain reaction ; STAT3 ; activation of signal transducer and activator of transcription-3 ; UTR ; 3&prime ; -untranslated region
• 刊名：Pathology - Research and Practice
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：213
• 期：2
• 页码：89-97
• 全文大小：1752 K
• 卷排序：213

文摘

MicroRNAs (miRNAs) are currently emerged as important regulators in psoriasis. Psoriasis is characterized by hyperproliferation and impaired differentiation of keratinocytes in skin lesions. miR-194 is a well-known regulator of cell proliferation and differentiation. However, the role of miR-194 in psoriasis pathogenesis remains unclear. In this study we aimed to investigate the role of miR-194 in keratinocyte hyperproliferation and differentiation. We found that miR-194 was significantly downregulated in psoriasis lesional skin. Overexpression of miR-194 inhibited the proliferation and promoted the differentiation of primary human keratinocytes, whereas miR-194 suppression promoted the proliferation and inhibited their differentiation. Bioinformatic analysis predicted that the Grainyhead-like 2 (GRHL2) was a target gene of miR-194, which we further validated with a dual-luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot analysis. The effect of miR-194 on cell proliferation and differentiation was significantly reversed by overexpression of GRHL2. Moreover, the expression of miR-194 and GRHL2 was inversely correlated in psoriasis lesional skin. Taken together, our results suggest that miR-194 inhibits the proliferation and promotes the differentiation of keratinocytes through targeting GRHL2. The downregulation of miR-194 expression may contribute to the pathogenesis of psoriasis and targeting miR-194 may represent a novel and potential therapeutic strategy for psoriasis.