Circular Rna Signatures Of Human Healing And Non-Healing Wounds

Venous leg ulcers (VUs) have a complex and obscure pathogenicity and effective VU therapies are still lacking. Circular RNAs (circRNAs) have emerged as powerful gene regulators with important roles in health and disease. Here, we used paired total RNA- and small RNA- sequencing to profile circRNAs,...

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Bibliographic Details
Published inJournal of investigative dermatology
Main Authors Toma, Maria A, Liu, Zhuang, Wang, Qizhang, Zhang, Letian, Li, Dongqing, Sommar, Pehr, Landén, Ning Xu
Format Journal Article
LanguageEnglish
Published United States 13.04.2022
Subjects
wound healing
circular RNA
transcriptome
chronic wound
microRNA
venous ulcer
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Summary:Venous leg ulcers (VUs) have a complex and obscure pathogenicity and effective VU therapies are still lacking. Circular RNAs (circRNAs) have emerged as powerful gene regulators with important roles in health and disease. Here, we used paired total RNA- and small RNA- sequencing to profile circRNAs, protein coding mRNAs, and microRNAs expression in a unique collection of clinical samples: healthy skin and acute wounds at inflammatory and proliferative phases, and wound-edge VU biopsies. We unravel a dynamically changed expression pattern of circRNAs during human skin repair and their abnormal expression signature in VU, which are presented as a searchable web resource (www.xulandenlab.com/humanwounds-circrna). We analyzed the co-expression relationship between the circRNAs and mRNAs with weighted correlation network analysis (WGCNA) and constructed circRNA-mRNA-miRNA networks. This allowed us to expose regulatory networks specific to the inflammatory and proliferative phases of wound repair and VU, the biological processes the circRNAs may regulate, and the circRNAs that could sponge miRNAs in human wounds. Importantly, we found that hsa-CHST15_0003 and hsa-TNFRSF21_0001, two circRNAs upregulated in VU, hampered epidermal keratinocyte migration while promoting proliferation through modulating gene networks underpinning these cellular processes. This study paves the way to decipher the functional significance of circRNAs in tissue repair.
ISSN:1523-1747