Publication Date:
2015-08-29
Description:
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.
Print ISSN:
0305-1048
Electronic ISSN:
1362-4962
Topics:
Biology
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