期刊
ADVANCES IN WOUND CARE
卷 9, 期 4, 页码 145-160出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/wound.2019.0956
关键词
noncoding RNA; wound healing; keratinocyte; circular RNA; diabetic foot ulcer
类别
资金
- Karolinska Institute
- Karolinska University Hospital
- Swedish Research Council (Vetenskapsradet) [2015-06246, 2016-02051]
- Ragnar Soderbergs Foundation [M31/15]
- Hedlunds Foundation
- Welander and Finsens Foundation (Hudfonden)
- Ake Wibergs Foundation
- Jeanssons Foundation
- Swedish Psoriasis Foundation
- Ming Wai Lau Centre for Reparative Medicine
- Tore Nilsons Foundation
- Lars Hiertas Foundation
- Karolinska Institutet
- National Natural Science Foundation of China [81611130075]
- Natural Fund of the Liaoning Provincial Science and Technology Department [20180530070]
- Vinnova [2016-02051] Funding Source: Vinnova
- Swedish Research Council [2016-02051, 2015-06246] Funding Source: Swedish Research Council
Objective: Insufficient knowledge about the molecular pathology of diabetic foot ulcer (DFU) impedes the development of effective wound treatment. Circular RNAs (circRNAs) are a novel class of RNA recently discovered to be widely expressed and have important biological functions; however, their role in skin wound healing remains largely unexplored. In this study, we investigated the role of circRNAs in DFU. Approach: CircRNA expression was profiled in normal wounds (NWs) and DFUs by microarray analysis, and hsa_circ_0084443 was identified as differentially expressed. The circularity and subcellular localization of hsa_circ_0084443 were characterized by northern blotting, real-time PCR, and fluorescence in situ hybridization. Cell migration, cell growth, and the transcriptome of human primary keratinocytes were analyzed after overexpression or RNA interference of hsa_circ_0084443. Results: hsa_circ_0084443 is downregulated in NWs compared with intact skin, and its level is higher in DFUs than NWs. We confirmed its circularity and presence in the cytoplasm of human epidermal keratinocytes. We showed that hsa_circ_0084443 reduced motility while enhancing the growth of keratinocytes. Furthermore, we identified a gene network with the potential to mediate the biological effect of hsa_circ_0084443. Innovation: CircRNAs have a functional role and a potential clinical significance in skin wound healing. Conclusions: We identified hsa_circ_0084443, a circRNA downregulated during NW healing, as a negative regulator of keratinocyte migration. Higher levels of hsa_circ_0084443 were detected in DFU samples, suggesting that it plays a role in pathology. These findings pave the way to understanding the functional role of circRNAs in human skin wound healing.
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