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Hsa-miR-877-5p Expression in Acute Ischemic Stroke Based on Bioinformatics Analysis and Clinical Validation

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Abstract

Inflammation and immunity play important roles in the pathogenesis of ischemic stroke. This study aimed to explore key regulatory genes in acute ischemic stroke (AIS) and their underlying mechanisms to provide new research targets for the diagnosis and treatment of ischemic stroke. We searched for differentially expressed mRNAs and miRNAs in patients with AIS and healthy populations in GEO databases, constructed a miRNA–mRNA network, and screened key miRNAs using least absolute shrinkage and selection operator regression and the support vector machine-recursive feature elimination model. Correlations between key miRNAs and infiltrating immune cells and inflammatory factors were analyzed using CIBERSORT and immunoassays and verified using clinical experiments. Bioinformatics analysis identified hsa-miR-877-5p as a key regulatory miRNA in AIS that can modulate immune and inflammatory responses. In clinical studies, it was verified by quantitative PCR analysis that the expression of hsa-miR-877-5p in the blood of AIS patients was higher than that of the healthy group. Then, enzyme-linked immunosorbent assay revealed that the expression of IL-23 and TNF-α related to inflammation in AIS patients was higher than that of the healthy. Quantitative PCR further found that the relative mRNA expression of IL-23, CXCR3, and TNF-α in AIS group was higher than that of the healthy group. This study may provide a basis for a more comprehensive understanding of the potential mechanism of the occurrence and development of AIS, and hsa-miR-877-5p and its downstream effectors IL-23, CXCR3, and TNF-α may be potential intervention targets in AIS.

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Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available due to protect patient privacy but are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.

Funding

This study was funded by the Natural Science Foundation of China (82205064) and the Natural Science Foundation of Shandong Province (ZR2021QH110).

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Authors and Affiliations

  1. Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road No.16369 in Lixia District, Jinan, China

    Si-Shuo Zhang, Wen-Qiang Cui, Hong-Wei Zhi, Hai-Tao Li, Hong-Yun Wu & Ya-Han Wang

  2. School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, University Road NO.4655 in Changqing District, Jinan, China

    Ji-Wei Zhang

  3. First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, University Road NO.4655 in Changqing District, Jinan, China

    Kai-Xin Zhang

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Si-Shuo Zhang, Ji-Wei Zhang, Kai-Xin Zhang, Wen-Qiang Cui, Hong-Wei Zhi, Hai-Tao Li, and Hong-Yun Wu. The first draft of the manuscript was written by Ya-Han Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ya-Han Wang.

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The authors declare no competing interests.

Ethics Approval

Human experimentations in this study was approved by the Ethics Committee of our hospital, and all enrolled subjects signed informed consent (Date: 2023/06/20/No. 2023-066-KY).

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the First Clinical Medical School of Shandong University of Chinese Medicine (Date: 2022/07/12/No. SDUTCM20220712001).

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Written informed consent was obtained from the clinical participants.

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Si-Shuo Zhang, Ji-Wei Zhang and Kai-Xin Zhang are the co-first authors.

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Zhang, SS., Zhang, JW., Zhang, KX. et al. Hsa-miR-877-5p Expression in Acute Ischemic Stroke Based on Bioinformatics Analysis and Clinical Validation. Mol Neurobiol 61, 1990–2005 (2024). https://doi.org/10.1007/s12035-023-03675-3

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