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Analysis of expression profiles and bioinformatics suggests that plasma exosomal circular RNAs may be involved in ischemic stroke in the Chinese Han population

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Abstract

Circular RNAs (circRNAs) have been confirmed to be associated with ischemic stroke(IS), but the involvement of exosomal circRNAs in plasma still needs to be extensively discussed. Therefore, we aimed to investigate the expression profile of exosomal circRNAs in plasma and the potential roles and mechanisms of exosomal circRNAs in the pathogenesis of ischemic stroke in the Chinese Han population. In this study, the plasma exosomal circRNA expression profiles of three IS patients and three healthy controls were analyzed using circRNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and circRNA-miRNA-mRNA regulatory network analysis were performed for the aberrantly expressed genes. Protein–protein interaction (PPI) networks and molecular complex detection algorithms (MCODEs) were analyzed by STRING and Cystoscope for functional annotation and construction, respectively. RNA-Seq analysis revealed that a total of 3540 circRNAs were aberrantly expressed in exosomes, 1177 circRNAs were significantly upregulated, and 2363 circRNAs were downregulated in IS patients compared to healthy controls. Bioinformatics analysis revealed that the parental genes of differentially expressed circRNAs as well as the mRNAs predicted in the circRNA-miRNA-mRNA regulatory network are enriched for signaling pathways associated with IS pathology, such as the MAPK signaling pathway, lipid and atherosclerosis, neurotrophic factor signaling pathways, mTOR signaling pathway, the p53 signaling pathway etc. Then, 10 hub genes were identified from the PPI and module networks, including FBXW11, FBXW7, UBE2V2, ANAPC7, CDC27, UBC, CDC5L, POLR2H, POLR2F and RBX1. Overall, the present study provides evidence of an altered plasma exosomal circRNA expression profile and its potential function in IS. Our findings may contribute to the study of the pathogenesis of circRNAs in IS and provide ideas for studying potential diagnostic biomarkers and therapeutic targets for IS.

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Availability of data and materials

The analyzed data sets generated during the study are available from the corresponding authors on reasonable request.

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Acknowledgements

The study was jointly supported by Guangxi Medical University and Guangxi University of Chinese Medicine.

Funding

This work was supported by The National Natural Science Foundation of China (No. 82160849 and 81874395).

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Author notes

  1. Bingyi Xu, Xianli Huang and Yan Yan contributed equally to this work.

Authors and Affiliations

  1. School of Public Health, Guangxi Medical University, Nanning, China

    Bingyi Xu, Zhi Zhao, Jialei Yang, Lulu Zhu & Li Su

  2. First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China

    Xianli Huang, Yan Yan, Yibing Yang, Baoyun Liang & Lian Gu

Authors
  1. Bingyi Xu
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  2. Xianli Huang
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  3. Yan Yan
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  4. Zhi Zhao
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  6. Lulu Zhu
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  9. Lian Gu
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  10. Li Su
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Contributions

Conception and design: Lian Gu, Li Su; Administrative support: Lian Gu, Li Su; Provision of study materials: Zhi Zhao, Jialei Yang; Collection and assembly of data: Lulu Zhu, Yibing Yang, Baoyun Liang; Data analysis and interpretation: Bingyi Xu, Xianli Huang, Yan Yan; Manuscript writing: Bingyi Xu, Xianli Huang, Yan Yan; Final approval of manuscript: All authors read and approved the final manuscript.

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Correspondence to Lian Gu or Li Su.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional. Informed consent forms were obtained from all study participants. The study protocol was approved by the ethical committee of Guangxi Medical University and the Ethics Committee of Guangxi University of Chinese Medicine. All methods were performed in accordance with the relevant guidelines and regulations.

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Xu, B., Huang, X., Yan, Y. et al. Analysis of expression profiles and bioinformatics suggests that plasma exosomal circular RNAs may be involved in ischemic stroke in the Chinese Han population. Metab Brain Dis 37, 665–676 (2022). https://doi.org/10.1007/s11011-021-00894-2

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