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Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration
Karolinska Inst, Ctr Mol Med, Dept Med Solna, Dermatol & Venereol Div, S-17176 Stockholm, Sweden.
Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
Karolinska Inst, Ctr Mol Med, Dept Med Solna, Dermatol & Venereol Div, S-17176 Stockholm, Sweden.
Karolinska Inst, Ctr Mol Med, Dept Med Solna, Dermatol & Venereol Div, S-17176 Stockholm, Sweden.
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2019 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 19, p. 9443-9452Article in journal (Refereed) Published
Abstract [en]

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-beta 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.

Place, publisher, year, edition, pages
2019. Vol. 116, no 19, p. 9443-9452
Keywords [en]
wound healing, long noncoding RNA, keratinocyte migration
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-384069DOI: 10.1073/pnas.1814097116ISI: 000467226400044PubMedID: 31019085OAI: oai:DiVA.org:uu-384069DiVA, id: diva2:1318839
Funder
Swedish Research Council, 2015-06246Swedish Research Council, 2016-02051Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-05-28Bibliographically approved

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