Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Genome-wide, integrative analysis of microRNA-mediated gene regulation in human wounds reveals cooperating microRNAs as therapeutic targets

Zhuang Liu, Letian Zhang, Maria-Alexandra Toma, Dongqing Li, Xiaowei Bian, Irena Pastar, Marjana Tomic-Canic, Pehr Sommar, View ORCID ProfileNing Xu Landén
doi: https://doi.org/10.1101/2021.12.17.473103
Zhuang Liu
1Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Letian Zhang
1Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria-Alexandra Toma
1Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dongqing Li
1Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
2Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaowei Bian
1Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irena Pastar
3Wound Healing and Regenerative Medicine Research Program, Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marjana Tomic-Canic
3Wound Healing and Regenerative Medicine Research Program, Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pehr Sommar
4Department of Plastic and Reconstructive Surgery, Karolinska University Hospital, Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ning.xu@ki.se pehr.sommar@regionstockholm.se
Ning Xu Landén
1Dermatology and Venereology Division, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden
5Ming Wai Lau Centre for Reparative Medicine, Stockholm Node, Karolinska Institute, 17177 Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ning Xu Landén
  • For correspondence: ning.xu@ki.se pehr.sommar@regionstockholm.se
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

MicroRNAs (miR), as important epigenetic control factors, reportedly regulate wound repair. However, our insufficient knowledge of clinically relevant miRs hinders their potential therapeutic use. For this, we performed miR and mRNA paired expression profiling in human acute wounds and chronic non-healing venous ulcers (VU) and presented our findings on a browsable web portal (http://130.229.28.87/shiny/miRNA_Xulab/). Integrative miR and mRNA-omics analysis unraveled miR-mediated gene regulatory networks in each repair phase of the wound repair process. Importantly, we identified 17 pathologically relevant miRs exhibiting abnormal expression in VU and displaying their targetome enriched in the VU gene signature. Study of the targetome and functions of eight clinically relevant miRs in skin cells revealed that the miRs upregulated in VU (i.e., miR-34a/c-5p, miR-424-5p, miR-450-5p, miR-7704, and miR-516-5p) promoted inflammation but inhibited proliferation. In contrast, the miRs downregulated in VU (i.e., miR-218-5p and miR-96-5p) were required for cell growth and activation. Moreover, we demonstrated miR-34a, miR-424, and miR-516 cooperativity in regulating keratinocyte growth and inflammatory response. Collectively, our study suggests that VU-dysregulated miRs cooperatively contribute to stalled wound healing characterized by failed transition from inflammatory-to-proliferative phase. Targeting cooperating miRNAs provide mew opportunity for development of clinically-relevant targeted therapy to attain higher therapeutic efficacy and specificity.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Co-senior authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted December 17, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome-wide, integrative analysis of microRNA-mediated gene regulation in human wounds reveals cooperating microRNAs as therapeutic targets
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome-wide, integrative analysis of microRNA-mediated gene regulation in human wounds reveals cooperating microRNAs as therapeutic targets
Zhuang Liu, Letian Zhang, Maria-Alexandra Toma, Dongqing Li, Xiaowei Bian, Irena Pastar, Marjana Tomic-Canic, Pehr Sommar, Ning Xu Landén
bioRxiv 2021.12.17.473103; doi: https://doi.org/10.1101/2021.12.17.473103
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Genome-wide, integrative analysis of microRNA-mediated gene regulation in human wounds reveals cooperating microRNAs as therapeutic targets
Zhuang Liu, Letian Zhang, Maria-Alexandra Toma, Dongqing Li, Xiaowei Bian, Irena Pastar, Marjana Tomic-Canic, Pehr Sommar, Ning Xu Landén
bioRxiv 2021.12.17.473103; doi: https://doi.org/10.1101/2021.12.17.473103

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4243)
  • Biochemistry (9173)
  • Bioengineering (6806)
  • Bioinformatics (24064)
  • Biophysics (12157)
  • Cancer Biology (9565)
  • Cell Biology (13825)
  • Clinical Trials (138)
  • Developmental Biology (7659)
  • Ecology (11737)
  • Epidemiology (2066)
  • Evolutionary Biology (15544)
  • Genetics (10672)
  • Genomics (14362)
  • Immunology (9515)
  • Microbiology (22906)
  • Molecular Biology (9130)
  • Neuroscience (49144)
  • Paleontology (358)
  • Pathology (1487)
  • Pharmacology and Toxicology (2584)
  • Physiology (3851)
  • Plant Biology (8351)
  • Scientific Communication and Education (1473)
  • Synthetic Biology (2301)
  • Systems Biology (6206)
  • Zoology (1303)