Circular RNA expression and clinical significance in peripheral blood mononuclear cells from acute ischemic stroke patients

尹巧  蒋文群 林世豪 郭思静 高丽 马伟伟 胡琴

doi:10.16098/j.issn.0529-1356.2026.02.001

PDF(2753 KB)

Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (2) : 143-152. DOI: 10.16098/j.issn.0529-1356.2026.02.001

Circular RNA expression and clinical significance in peripheral blood mononuclear cells from acute ischemic stroke patients

YIN Qiao¹, JIANG Wen-qun², LIN Shi-hao¹, GUO Si-jing¹, GAO Li³, MA Wei-wei ^4*, HU Qin^1*

Author information +

History +

Abstract

Objective To characterize the expression profiles and potential biological functions of circular RNAs (circRNAs) in peripheral blood mononuclear cells (PBMCs) from patients with acute ischemic stroke (AIS), and to evaluate their clinical relevance for diagnostic and prognostic applications. Methods Transcriptome-wide RNA sequencing was performed on PBMC samples collected from AIS patients (n=5) and age- and sex-matched healthy controls (n=5) in a discovery cohort to delineate the circRNA landscape in AIS. The top ten differentially expressed circRNAs (DECs) were identified based on fold change and statistical significance. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to explore the biological functions of the host genes of these DECs. Validation of candidate circRNAs was performed using Real-time PCR in an independent validation cohort consisting of 30 AIS patients and matched controls. The diagnostic and prognostic significance of validated circRNAs was further assessed through correlation analyses with National Institutes of Health Stroke Scale (NIHSS) scores and receiver operating characteristic (ROC) curve analysis. Results Functional enrichment analysis revealed that the host genes of the top DECs were predominantly involved in immune responses, protein degradation and cell death. Among the candidates, hsa_circ_0075436 and hsa_circ_0005729 were significantly downregulated in AIS patients as validated by Real-time PCR. Importantly, their expression levels were inversely correlated with NIHSS scores at both admission and discharge, suggesting a potential link to disease severity and neurological recovery. ROC analysis demonstrated that both circRNAs exhibited robust diagnostic performance, highlighting their potential as blood-based biomarkers. Conclusion The host genes of DECs are involved in key pathways related to transcriptional regulation, protein ubiquitination, immune response, protein degradation, and apoptosis. Among them, hsa_circ_0075436 and hsa_circ_0005729 represent promising candidates for further development as diagnostic and prognostic biomarkers in acute ischemic stroke.

Key words

Acute ischemic stroke

/ Circular RNA;Peripheral blood mononuclear cell / Biomarker；Whole transcriptome sequencing / Real-time PCR / Human

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

YIN Qiao, JIANG Wen-qun, LIN Shi-hao, GUO Si-jing, GAO Li, MA Wei-wei , HU Qin. Circular RNA expression and clinical significance in peripheral blood mononuclear cells from acute ischemic stroke patients[J]. Acta Anatomica Sinica. 2026, 57(2): 143-152 https://doi.org/10.16098/j.issn.0529-1356.2026.02.001

References

［1］ Ahmed MG, Shaheen N, Shaheen A, et al. Outcomes of endovascular treatment alone or with intravenous alteplase in acute ischemic stroke patients: a retrospective cohort study［J］. Brain Hemorrhages, 2024，5(1): 21-28.

［2］ Li SD, Wang AX, Shi L, et al. Safety and efficacy of Angong Niuhuang Pills in patients with moderate-to-severe acute ischemic stroke (ANGONG TRIAL): a randomized double-blind placebo-controlled pilot clinical trial［J］. Chin Med J (Engl), 2025,138(5):579-588.

［3］ Czap AL, Sheth SA. Overview of imaging modalities in stroke［J］. Neurology, 2021, 97(20 Suppl 2):S42-S51.

［4］ Simpkins AN, Janowski M, Oz HS, et al. Biomarker application for precision medicine in stroke［J］. Transl Stroke Res, 2020,11(4): 615-627.

［5］ Dong J, Zeng Z, Huang Y, et al. Challenges and opportunities for circRNA identification and delivery［J］. Crit Rev Biochem Mol Biol, 2023, 58(1): 19-35.

［6］ Xu F, Xiao Q, Du WW, et al. CircRNA: functions, applications and prospects［J］. Biomolecules, 2024,14(12):1503.

［7］ Zhou WY, Cai ZR, Liu J, et al. Circular RNA: metabolism, functions and interactions with proteins［J］. Mol Cancer, 2020,19(1): 172.

［8］ Meng S, Zhou H, Feng Z, et al. CircRNA: functions and properties of a novel potential biomarker for cancer［J］. Mol Cancer, 2017,16(1):94.

［9］ Enuka Y, Mattia L, Morris EF, et al. Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor［J］. Nucleic Acids Res, 2016, 44(3): 1370-1383.

［10］ Chen XL,Tan QD, Chen KJ, et al.CircRNA and stroke: new insight of potential biomarkers and therapeutic targets［J］. Neurochem Res, 2024, 49(3): 557-567.

［11］ Gu T, Tan QD, Chen KJ, et al.The impact of centrifugal force on isolation of bone marrow mononuclear cells using density gradient centrifugation［J］. Aesthetic Plast Surg, 2024,48(9): 1855-1866.

［12］Çｏｒｂａｃıｏɡ̆ｌｕ ŞＫ, Aksel G. Receiver operating characteristic curve analysis in diagnostic accuracy studies: a guide to interpreting the area under the curve value［J］. Turk J Emerg Med, 2023, 23(4): 195-198.

［13］ Liu X., Yu Z, Shurong Z, et al. Circular RNA: an emerging frontier in RNA therapeutic targets, RNA therapeutics, and mRNA vaccines［J］. J Control Release, 2022, 348: 84-94.

［14］ Misir S, Wu N, Yang BB. Specific expression and functions of circular RNAs［J］. Cell Death Differ, 2022, 29(3): 481-491.

［15］ Xu Z, Yang F, Zheng L.Uncovering the dual roles of peripheral immune cells and their connections to brain cells in stroke and post-stroke stages through single-cell sequencing［J］. Front Neurosci, 2024, 18:1443438.

［16］ Mohammad TAM, Al-Haideri M, Al-Naqshabandi AA.Decoding the immune response: analyzing PBMCs in ischemic stroke and evaluating the effects of Rivaroxaban on gene expression［J］. Hum Immunol, 2025, 86(2):111252.

［17］ Otsu Y, Hatakeyama M, Kanayama T, et al.Oxygen-glucose deprived peripheral blood mononuclear cells protect against ischemic stroke［J］. Neurotherapeutics, 2023, 20(5): 1369-1387.

［18］ Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms［J］. CNS Neurosci Ther, 2021, 27(1): 36-47.

［19］ Zu J, Zuo L, Zhang Z, et al. Circular RNA FUNDC1 for prediction of acute phase outcome and long-term survival of acute ischemic stroke［J］. Front Neurol, 2022, 13: 846198.

［20］ Liu Y, Li Y, Zang J, et al. CircOGDH is a penumbra biomarker and therapeutic target in acute ischemic stroke［J］. Circ Res, 2022, 130(6): 907-924.

［21］ Zuo L, Zhang L, Zu J, et al. Circulating circular RNAs as biomarkers for the diagnosis and prediction of outcomes in acute ischemic stroke［J］. Stroke, 2020, 51(1): 319-323.

［22］ Lu Y, Huang J, Ying X, et al. RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy［J］. Signal Transduct Target Ther, 2022, 7(1): 185.

［23］ Locke AJ, Farraj RA, Tran C, et al. The role of RNF138 in DNA end resection is regulated by ubiquitylation and CDK phosphorylation［J］. J Biol Chem, 2024, 300(3): 105709.

［24］ Halim DO, Krishnan G, Hass EP, et al. The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD［J］. Cell Rep, 2024,43(7): 114375.

［25］ Van Bergen NJ, Ahmed SM, Collins F, et al. Mutations in the exocyst component EXOC2 cause severe defects in human brain development［J］. J Exp Med, 2020,217(10):e20192040.