Abstract
Infection with the human papillomavirus (HPV) is a common occurrence among the global population, with millions of new cases emerging on an annual basis. Dysregulated microRNA (miRNA) expression is increasingly being identified to play a role in a number of different diseases, especially in the context of high-risk HPV infection. The present study investigated the miRNA expression profiles of warts induced by low-risk HPV. In warts, miR-27b, miR-24-1, miR-3654, miR-647, and miR-1914 were downregulated while miR-612 was upregulated compared to normal skin. Using miRTargetLink Human, experimentally supported evidence was obtained showing that miR-27b targeted the vascular endothelial growth factor C (VEGFC) and CAMP-responsive element binding protein 1 (CREB1) genes. The VEGFC and CREB1 genes have been reported to be involved in tumorigenesis and wart formation, respectively. Similarly, the oxidized low-density lipoprotein receptor 1 (OLR1) gene, which plays an important role in the humoral immunity of the skin, and the plexin D1 (PLXND1) gene, which is highly expressed in tumor vasculature, were both found to be common targets of miR-27b, miR-1914, and miR-612.
Highlights
Human skin is an integumentary organ that consists of two main layers, the outermost epidermis and the underlying dermis, connected by the basement membrane [1]
The fold change for each of the 12 control and 12 wart samples was individually plotted for the 6 Differentially expressed (DE) miRNAs, and an overall consistent DE of the latter was shown in the wart samples (Figure S1)
MiR-27b was found to be upregulated in warts compared to normal skin, and this miRNA displayed the highest number of interactions (n = 27) with target genes. miR-27b, one of two miR-27 homologs, modulates adipocyte differentiation as well as adipogenesis regulation by targeting peroxisome proliferator-activated receptor gamma (PPARγ) [31]
Summary
Human skin is an integumentary organ that consists of two main layers, the outermost epidermis and the underlying dermis, connected by the basement membrane [1]. The multilayered epidermis is predominantly made up of keratinocyte cells that originate in its basal layer and function to create a physical barrier against environmental and pathogenic threats [2]. Keratinocytes faced with invasion by pathogens can induce apoptosis, trigger inflammatory responses, and produce various types of antimicrobial peptides as a means of innate immune defense [3,4,5]. One pathogen that exclusively targets keratinocytes found in the basal epidermal layer is the human papillomavirus (HPV) [6]. As the most common sexually transmitted infection, HPV infects millions of people each year and can be spread by skin-to-skin contact [7].
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