Micro RNA ‐23b‐3p regulates human keratinocyte differentiation through repression of TGIF 1 and activation of the TGF ‐ß– SMAD 2 signalling pathway

Micro RNA s (mi RNA s) are a class of short non‐coding RNA s capable of repressing gene expression at the post‐transcriptional level. mi RNA s participate in the control of numerous cellular mechanisms, including skin homeostasis and epidermal differentiation. However, few mi RNA s 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 mi R ‐23b‐3p, a mi RNA that is expressed during the late step of human keratinocyte differentiation. We report that mi R ‐23b‐3p silencing modulates epidermal differentiation in human skin reconstructs. The SMAD transcriptional corepressor TGIF 1 was identified on bioinformatic analysis as a potential target of mi R ‐23b‐3p. Expression analysis and reporter gene assays confirmed direct regulation of TGIF 1 expression by mi R ‐23b‐3p. Finally, we showed that mi R ‐23‐3p was able to activate TGF ‐ß signalling in human keratinocytes by increasing SMAD 2 phosphorylation through TGIF 1 repression. Taken together, these data identify mi R ‐23b‐3p as a new regulator of human epidermal differentiation in line with TGF ‐ß signalling.