MicroRNA-23b-3p regulates human keratinocyte differentiation through repression of TGIF1 and activation of the TGF-ß-SMAD2 signalling pathway

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• 作者：Laetitia Barbollat-Boutrand ; Nicolas Joly-Tonetti ; Morgan Dos Santos ; Elodie Metral ; Aur&eacute ; lie Boher ; Ingrid Masse ; Odile Berthier-Vergnes ; Philippe Bertolino ; Odile Damour and J&eacute ; rô ; me Lamartine
• 刊名：Experimental Dermatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：26
• 期：1
• 页码：51-57
• 全文大小：716K
• ISSN：1600-0625

文摘

MicroRNAs (miRNAs) are a class of short non-coding RNAs capable of repressing gene expression at the post-transcriptional level. miRNAs participate in the control of numerous cellular mechanisms, including skin homeostasis and epidermal differentiation. However, few miRNAs involved in these processes have been identified so far in human skin, and the gene networks they control remain largely unknown. Here, we focused on miR-23b-3p, a miRNA that is expressed during the late step of human keratinocyte differentiation. We report that miR-23b-3p silencing modulates epidermal differentiation in human skin reconstructs. The SMAD transcriptional corepressor TGIF1 was identified on bioinformatic analysis as a potential target of miR-23b-3p. Expression analysis and reporter gene assays confirmed direct regulation of TGIF1 expression by miR-23b-3p. Finally, we showed that miR-23-3p was able to activate TGF-ß signalling in human keratinocytes by increasing SMAD2 phosphorylation through TGIF1 repression. Taken together, these data identify miR-23b-3p as a new regulator of human epidermal differentiation in line with TGF-ß signalling.