?Np63 intronic miR-944 is implicated in the ?Np63-mediated induction of epidermal differentiation.

ABSTRACT: ?Np63 is required for both the proliferation and differentiation of keratinocytes, but its role in the differentiation of these cells is poorly understood. The corresponding gene, TP63, harbors the MIR944 sequence within its intron. However, the mechanism of biogenesis and the function of miR-944 are unknown. We found that miR-944 is highly expressed in keratinocytes, in a manner that is concordant with that of ?Np63 mRNA, but the regulation of miR-944 expression under various conditions did not correspond with that of ?Np63. Bioinformatics analysis and functional studies demonstrated that MIR944 has its own promoter. We demonstrate here that MIR944 is a target of ?Np63. Promoter analysis revealed that the activity of the MIR944 promoter was markedly enhanced by the binding of ?Np63, which was maintained by the supportive action of AP-2 during keratinocyte differentiation. Our results indicated that miR-944 biogenesis is dependent on ?Np63 protein, even though it is generated from ?Np63 mRNA-independent transcripts. We also demonstrated that miR-944 induces keratin 1 and keratin 10 expression by inhibiting ERK signaling and upregulating p53 expression. Our findings suggested that miR-944, as an intronic miRNA and a direct target of ?Np63, contributes to the function of ?Np63 in the induction of epidermal differentiation.

SUBMITTER: Kim KH 

PROVIDER: S-EPMC4551945 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature