Effect of miR-939 overexpression on gene expression in heat-killed S. aureus-stimulated keratinocytes
Atopic dermatitis (AD) is a common, chronic inflammatory skin disease that seriously affects quality of life and is a major cause of skin diseases worldwide. Staphylococcus aureus (S. aureus) colonization on the skin plays an important role in the pathogenesis of AD; however, the mechanism of how it modulates skin immunity to exacerbate AD remains unclear. MicroRNAs are short non-coding RNAs that act as post-transcriptional regulators of genes. They are involved in the pathogenesis of various inflammatory skin diseases. In this study, we established miRNA expression profiles for keratinocytes stimulated with heat-killed S. aureus (HKSA). We found that miR-939 was highly upregulated in HKSA-stimulated keratinocytes and AD lesions. In vitro studies revealed that miR-939 increased the expression of matrix metalloproteinase genes, including MMP1, MMP3, and MMP9, as well as the cell adhesion molecule ICAM1 in human primary keratinocytes. In vivo studies indicated that miR-939 increased the expression of matrix metalloproteinases to promote the colonization of S. aureus and exacerbated S. aureus-induced AD-like skin inflammation. Taken together, these findings suggest that miR-939 is an important regulator of skin inflammation in AD. Overall design: To perform an unbiased study of miR-939 function in keratinocytes, we performed a global transcriptomic analysis in keratinocytes with miR-939 overexpression followed by HKSA stimulation. Keratinocytes transfected with hsa-miR-939-5p mimic or the corresponding negative control, followed by treatment with HKSA or PBS for 8 h were subject to RNA sequencing.