The major miR-31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation

Abstract

Emerging evidence indicates that even subtle changes in the expression of key genes of signaling pathways can have profound effects. MicroRNAs (miRNAs) are masters of subtleness and generally have only mild effects on their target genes. The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions associated with activated keratinocytes such as the hyperproliferative diseases psoriasis, non-melanoma skin cancer, and hair follicle growth. miR-31 is a marker of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the function of keratinocytes, subsequently leading to aberrant proliferation, apoptosis and differentiation that result in altered hair growth, while loss of miR-31 leads to increased hair growth. Through in vitro and in vivo studies, we have defined a set of conserved miR-31 target genes, including LATS2 and STK40, which serve as new players in the regulation of keratinocyte growth and hair follicle biology. LATS2 can regulate growth of keratinocytes, while we have identified a function of STK40 in promoting the expression of key hair follicle program regulators such as HR, DLX3, and HOXC13.

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