Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration.
keratinocyte migration
long noncoding RNA
wound healing
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
07 05 2019
07 05 2019
Historique:
pubmed:
26
4
2019
medline:
17
3
2020
entrez:
26
4
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31019085
pii: 1814097116
doi: 10.1073/pnas.1814097116
pmc: PMC6511036
doi:
Substances chimiques
E2F1 Transcription Factor
0
E2F1 protein, human
0
RNA, Long Noncoding
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9443-9452Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Trends Genet. 2018 Feb;34(2):142-157
pubmed: 29249332
Sci Transl Med. 2014 Dec 3;6(265):265sr6
pubmed: 25473038
Oncogene. 2001 May 28;20(24):3139-55
pubmed: 11420731
J Biol Chem. 2002 Mar 22;277(12):10626-32
pubmed: 11790795
BMC Genomics. 2013 Sep 24;14:651
pubmed: 24063787
Cell. 2013 Jun 6;153(6):1281-95
pubmed: 23706625
Adv Wound Care (New Rochelle). 2014 Jul 1;3(7):445-464
pubmed: 25032064
Genes Dev. 2012 Feb 15;26(4):338-43
pubmed: 22302877
Nature. 2013 Jan 10;493(7431):231-5
pubmed: 23201690
Pflugers Arch. 2016 Jun;468(6):935-43
pubmed: 26935426
Mol Cell Proteomics. 2014 Feb;13(2):397-406
pubmed: 24309898
Hum Mol Genet. 2015 Nov 1;24(21):6240-53
pubmed: 26307088
Eur Surg Res. 2012;49(1):35-43
pubmed: 22797712
Genome Res. 2012 Aug;22(8):1407-18
pubmed: 22684279
Nat Rev Mol Cell Biol. 2000 Dec;1(3):169-78
pubmed: 11252892
Nature. 2010 Sep 23;467(7314):430-5
pubmed: 20720539
Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):E5261-70
pubmed: 26351698
J Biol Chem. 2006 Jul 14;281(28):19489-500
pubmed: 16682412
Mol Cell. 2008 Oct 24;32(2):232-46
pubmed: 18951091
J Biol Chem. 2017 Jul 28;292(30):12483-12495
pubmed: 28596382
Oncotarget. 2017 Jun 27;8(26):43470-43480
pubmed: 28415644
Cell Biosci. 2016 Jul 11;6:45
pubmed: 27408682
Nucleic Acids Res. 2015 Apr 30;43(8):4363-4
pubmed: 25829178
Elife. 2014 Nov 21;3:e04530
pubmed: 25415054
Nature. 2006 Feb 16;439(7078):871-4
pubmed: 16357870
Cell Res. 2015 Mar;25(3):335-50
pubmed: 25686699
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Genome Biol. 2011;12(2):R16
pubmed: 21324177
Adv Wound Care (New Rochelle). 2014 Jul 1;3(7):468-475
pubmed: 25032066
ACS Chem Biol. 2010 Feb 19;5(2):245-53
pubmed: 20020776
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W345-9
pubmed: 17631615
Methods Mol Biol. 2013;1037:255-64
pubmed: 24029940
Cell. 2011 Dec 9;147(6):1283-94
pubmed: 22153073
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nature. 2017 Aug 17;548(7667):343-346
pubmed: 28792927
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
Cell Rep. 2015 May 19;11(7):1110-22
pubmed: 25959816
Cell. 2018 Jan 25;172(3):393-407
pubmed: 29373828
Nature. 2013 Nov 21;503(7476):371-6
pubmed: 24107992
Diabet Med. 2002 Jun;19(6):440-7
pubmed: 12060054
Mol Pharmacol. 2002 Jul;62(1):65-74
pubmed: 12065756
Mol Cell. 2010 Sep 24;39(6):925-38
pubmed: 20797886
Nucleic Acids Res. 2007 Jan;35(Database issue):D358-62
pubmed: 17098935
Int J Burns Trauma. 2012;2(1):18-28
pubmed: 22928164
J Biol Chem. 2005 Jun 24;280(25):24159-67
pubmed: 15855153
Mol Med. 2010 Mar;16(3-4):92-101
pubmed: 20069132
Nature. 2012 Sep 6;489(7414):109-13
pubmed: 22955621
J Biomed Biotechnol. 2011;2011:969618
pubmed: 21151647
Science. 2017 Jan 6;355(6320):
pubmed: 27980086
PLoS Genet. 2013;9(12):e1003994
pubmed: 24367273
J Invest Dermatol. 2018 May;138(5):1187-1196
pubmed: 29273315