WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

J Invest Dermatol. 2019 Jun;139(6):1373-1384. doi: 10.1016/j.jid.2018.11.033. Epub 2018 Dec 27.


Chronic wounds represent a major and growing health and economic burden worldwide. A better understanding of molecular mechanisms of normal as well as impaired wound healing is needed to develop effective treatment. Herein we studied the potential role of long noncoding RNA LOC100130476 in skin wound repair. LOC100130476 is an RNA polymerase II-encoded polyadenylated transcript present in both cytoplasm and nucleus. We found that its expression was lower in wound-edge keratinocytes of human chronic wounds compared to normal wounds of healthy donors and intact skin. In cultured keratinocytes, LOC100130476 expression was induced by TGF-β signaling. By reducing LOC100130476 expression with antisense oligos or activating its transcription with CRISPR/Cas9 Synergistic Activation Mediator system, we showed that LOC100130476 restricted the production of inflammatory chemokines by keratinocytes, while enhancing cell migration. In line with this, knockdown of LOC100130476 impaired re-epithelization of human ex vivo wounds. Based on these results, we named LOC100130476 wound and keratinocyte migration-associated long noncoding RNA 2 (WAKMAR2). Moreover, we identified a molecular network that may mediate the biological function of WAKMAR2 in keratinocytes using microarray. In summary, our data suggest that WAKMAR2 is an important regulator of skin wound healing and its deficiency may contribute to the pathogenesis of chronic wounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Chemokines / genetics*
  • Chemokines / immunology
  • Chemokines / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology*
  • Gene Knockdown Techniques
  • Healthy Volunteers
  • Humans
  • Keratinocytes / physiology*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Primary Cell Culture
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Skin / immunology
  • Skin / injuries
  • Skin / pathology
  • Tissue Culture Techniques
  • Varicose Ulcer / genetics*
  • Varicose Ulcer / immunology
  • Varicose Ulcer / pathology
  • Wound Healing / genetics
  • Wound Healing / immunology
  • Young Adult


  • Chemokines
  • RNA, Long Noncoding
  • long non-coding RNA LOC100130476, human