Abstract
Lichen sclerosus (LS) is a chronic inflammatory skin disorder with unknown pathogenesis. The aberrant expression of microRNAs (miRNAs) is considered to exert a crucial role in LS. We used the next-generation sequencing technology (RNASeq) for miRNA profiling and Ingenuity Pathway Analysis (IPA) for molecular network analysis. We performed qRT-PCR, miRNA transfection and Matrigel assays for functional studies. We identified a total of 170 differentially expressed miRNAs between female LS and matched adjacent normal tissue using RNASeq, with 119 upregulated and 51 downregulated. Bioinformatics analysis revealed molecular networks that may shed light on the pathogenesis of LS. We verified the expression of a set of miRNAs that are related to autoimmunity, such as upregulated miR-326, miR-142-5p, miR-155 and downregulated miR-664a-3p and miR-181a-3p in LS tissue compared to the matched adjacent normal tissue. The differentially expressed miRNAs were also verified in blood samples from LS patients compared to healthy female volunteers. Functional studies demonstrated that a forced expression of miR-142-5p in human dermal fibroblast PCS-201-010 cells resulted in decreased cell proliferation and migration. These findings suggest that differentially expressed miRNAs may play an important role in LS pathogenesis; therefore, they could serve as biomarkers for LS management.
Highlights
Lichen sclerosus (LS) is the condition of chronic, lymphocyte-mediated inflammatory dermatitis that has a negative impact on quality of life and may proceed to malignant disease [1,2]
False Discovery Rate (FDR) multiple testing correction (p < 0.05) method and 1.5-fold change cut-off, we identified 170 miRNAs differentially expressed between LS and normal tissue, including 119 upregulated and 51 downregulated miRNAs (Figure 1)
As an attempt to establish whether miRNA profiling could be used as biomarker for LS, we investigated whether there is a similar miRNA expression pattern in peripheral blood samples
Summary
Lichen sclerosus (LS) is the condition of chronic, lymphocyte-mediated inflammatory dermatitis that has a negative impact on quality of life and may proceed to malignant disease [1,2]. LS can affect any part of the skin, but it most frequently occurs in the anogenital area, with a higher incidence of onset among premenarchal and post-menopausal females [3,4]. The typical lesions of vulvar LS are white plaques and papules, often with areas of ecchymosis, excoriation, and ulceration. Presenting symptoms may include intense pruritus, pain, burning and dyspareunia. Between 4 and 7% of women with LS develop vulvar squamous carcinoma [5]. LS is among one of the most common referrals for vulvar pruritus and is the most common cause of inflammatory structural changes to the vulvar region [6,7,8].
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