Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus
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...
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2021-09-01
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author | 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 |
author_facet | 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 |
author_sort | Xiaohui Tan |
collection | DOAJ |
description | 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. |
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language | English |
last_indexed | 2024-03-10T07:49:12Z |
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spelling | doaj.art-4a91457f755f444885e3f0c39025ff172023-11-22T12:23:48ZengMDPI AGCells2073-44092021-09-01109229110.3390/cells10092291Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen SclerosusXiaohui Tan0Shuyang Ren1Canyuan Yang2Shuchang Ren3Melinda Z. Fu4Amelia R. Goldstein5Xuelan Li6Leia Mitchell7Jill M. Krapf8Charles J. Macri9Andrew T. Goldstein10Sidney W. Fu11Departments 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, USADepartments 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, USADepartments 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, USADepartments 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, USADepartments 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, USADepartment of Biology, Duke University, Durham, NC 27708, USADepartment of OB/GYN, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, ChinaThe Center for Vulvovaginal Disorders, Washington, DC 20037, USAThe Center for Vulvovaginal Disorders, Washington, DC 20037, USAThe Center for Vulvovaginal Disorders, Washington, DC 20037, USAThe Center for Vulvovaginal Disorders, Washington, DC 20037, USADepartments 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, USALichen 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.https://www.mdpi.com/2073-4409/10/9/2291lichen sclerosusmiRNAgene networkpathogenesis |
spellingShingle | 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 Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus Cells lichen sclerosus miRNA gene network pathogenesis |
title | Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus |
title_full | Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus |
title_fullStr | Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus |
title_full_unstemmed | Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus |
title_short | Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus |
title_sort | differentially regulated mirnas and their related molecular pathways in lichen sclerosus |
topic | lichen sclerosus miRNA gene network pathogenesis |
url | https://www.mdpi.com/2073-4409/10/9/2291 |
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