SYSTEMATIC REVIEW article
Front. Bioinform.
Sec. RNA Bioinformatics
Altered circRNAs: A novel potential mechanism for the functions of extracellular vesicles derived from platelet-rich plasma
Provisionally accepted
- 1Nantong Hospital of Traditional Chinese Medicine, Nantong, China
- 2Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
- 3The Second Hospital of Jilin University, Changchun, China
- 4Second Affiliated Hospital of Jilin University, Changchun, China
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Platelet-rich plasma (PRP) has been widely applied in clinical practice for tissue repair and regeneration. Recent studies reported that lots of extracellular vesicles (EVs) derived from PRP (PRP-EVs) also participate in the functions of tissue repair and regeneration except for these secreted growth factors. However, the relevant mechanisms of PRP-EVs remain unknown. Here, we attempted to reveal the potential circular RNA mechanisms of PRP-EVs using high-throughput RNA sequencing (RNA-seq) technique and bioinformatics analysis. Six healthy donors were enrolled in this study, including three donors for the isolation of PRP-EVs and three donors for the isolation of EVs derived from blood plasma (Plasma-EVs). As a result, we confirmed that PRP activation by thrombin could significantly promote the formations and secretions of EVs, especially these EVs with a diameter ranging from 50 nm to 200 nm. Besides, 144 circRNAs were altered in PRP-EVs by a fold-change ≥ 2.0 and p-value ≤ 0.05. Among these, 89 circRNAs were up-regulated, while 55 circRNAs were down-regulated. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and circRNA-miRNA-mRNA interaction network were performed to predict the potential roles of circRNAs in PRP-EVs. GO analysis indicated that these altered circRNAs might be related to the physiological processes of cell genesis and development. The pathways which were most highly correlated with the biological functions of PRP-EVs were the TGF-beta signaling pathway and HIF-1 signaling pathway. Besides, the expression levels of five selected circRNAs were verified by RT-qPCR. In conclusion, for the first time, this study explained a novel potential mechanism of the biological functions of PRP-EVs in terms of the altered circRNAs. We believe that this study may lay the groundwork for the clinical application of PRP-EVs and provide the possible novel targets for further researches.
Keywords: circular RNA, extracellular vesicles, Platelet-Rich Plasma, Bioinformatics analysis, Potential mechanism
Received: 26 Aug 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Niu, Wang, Gao and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jun Zhang
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