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Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration
An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576,...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511036/ https://www.ncbi.nlm.nih.gov/pubmed/31019085 http://dx.doi.org/10.1073/pnas.1814097116 |
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author | Li, Dongqing Kular, Lara Vij, Manika Herter, Eva K. Li, Xi Wang, Aoxue Chu, Tongbin Toma, Maria-Alexandra Zhang, Letian Liapi, Eleni Mota, Ana Blomqvist, Lennart Sérézal, Irène Gallais Rollman, Ola Wikstrom, Jakob D. Bienko, Magda Berglund, David Ståhle, Mona Sommar, Pehr Jagodic, Maja Landén, Ning Xu |
author_facet | Li, Dongqing Kular, Lara Vij, Manika Herter, Eva K. Li, Xi Wang, Aoxue Chu, Tongbin Toma, Maria-Alexandra Zhang, Letian Liapi, Eleni Mota, Ana Blomqvist, Lennart Sérézal, Irène Gallais Rollman, Ola Wikstrom, Jakob D. Bienko, Magda Berglund, David Ståhle, Mona Sommar, Pehr Jagodic, Maja Landén, Ning Xu |
author_sort | Li, Dongqing |
collection | PubMed |
description | An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed “wound and keratinocyte migration-associated lncRNA 1” (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds. |
format | Online Article Text |
id | pubmed-6511036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-65110362019-05-23 Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration Li, Dongqing Kular, Lara Vij, Manika Herter, Eva K. Li, Xi Wang, Aoxue Chu, Tongbin Toma, Maria-Alexandra Zhang, Letian Liapi, Eleni Mota, Ana Blomqvist, Lennart Sérézal, Irène Gallais Rollman, Ola Wikstrom, Jakob D. Bienko, Magda Berglund, David Ståhle, Mona Sommar, Pehr Jagodic, Maja Landén, Ning Xu Proc Natl Acad Sci U S A PNAS Plus An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed “wound and keratinocyte migration-associated lncRNA 1” (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds. National Academy of Sciences 2019-05-07 2019-04-24 /pmc/articles/PMC6511036/ /pubmed/31019085 http://dx.doi.org/10.1073/pnas.1814097116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | PNAS Plus Li, Dongqing Kular, Lara Vij, Manika Herter, Eva K. Li, Xi Wang, Aoxue Chu, Tongbin Toma, Maria-Alexandra Zhang, Letian Liapi, Eleni Mota, Ana Blomqvist, Lennart Sérézal, Irène Gallais Rollman, Ola Wikstrom, Jakob D. Bienko, Magda Berglund, David Ståhle, Mona Sommar, Pehr Jagodic, Maja Landén, Ning Xu Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration |
title | Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration |
title_full | Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration |
title_fullStr | Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration |
title_full_unstemmed | Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration |
title_short | Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration |
title_sort | human skin long noncoding rna wakmar1 regulates wound healing by enhancing keratinocyte migration |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511036/ https://www.ncbi.nlm.nih.gov/pubmed/31019085 http://dx.doi.org/10.1073/pnas.1814097116 |
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