Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus
Xiaohui Tan,
Shuyang Ren,
Canyuan Yang,
Shuchang Ren,
Melinda Z. Fu,
Amelia R. Goldstein,
Xuelan Li,
Leia Mitchell,
Jill M. Krapf,
Charles J. Macri,
Andrew T. Goldstein,
Sidney W. Fu
Affiliations
Xiaohui Tan
Departments of Medicine (Division of Genomic Medicine), and of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, N.W., Ross Hall 402C, Washington, DC 20037, USA
Shuyang Ren
Departments of Medicine (Division of Genomic Medicine), and of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, N.W., Ross Hall 402C, Washington, DC 20037, USA
Canyuan Yang
Departments of Medicine (Division of Genomic Medicine), and of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, N.W., Ross Hall 402C, Washington, DC 20037, USA
Shuchang Ren
Departments of Medicine (Division of Genomic Medicine), and of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, N.W., Ross Hall 402C, Washington, DC 20037, USA
Melinda Z. Fu
Departments of Medicine (Division of Genomic Medicine), and of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, N.W., Ross Hall 402C, Washington, DC 20037, USA
Amelia R. Goldstein
Department of Biology, Duke University, Durham, NC 27708, USA
Xuelan Li
Department of OB/GYN, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
Leia Mitchell
The Center for Vulvovaginal Disorders, Washington, DC 20037, USA
Jill M. Krapf
The Center for Vulvovaginal Disorders, Washington, DC 20037, USA
Charles J. Macri
The Center for Vulvovaginal Disorders, Washington, DC 20037, USA
Andrew T. Goldstein
The Center for Vulvovaginal Disorders, Washington, DC 20037, USA
Sidney W. Fu
Departments of Medicine (Division of Genomic Medicine), and of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, N.W., Ross Hall 402C, Washington, DC 20037, USA
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.
