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CircRNA_102046 Affects the Occurrence and Development of Ischemic Stroke by Regulating the miR-493-5p/ROCK1 Signaling

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Abstract

In our previous studies, the results have revealed that circRNA_102046 is significantly upregulated in plasma of patients with ischemic stroke, which closely related to NIHSS score. Human neural stem cells (hNSCs) were used for characterization and subcellular localization of circRNA_102046, and hNSCs OGD/R model was generated. The proliferation of cells was examined by CCK-8 assay. The expression levels of associated molecules were evaluated using RT-qPCR, immunofluorescence staining or western blotting. The binding and co-localization of associated molecules were also evaluated by RIP and FISH assay. Furthermore, MCAO mouse model was established to examine the effects of circRNA_102046 on the progression of ischemic stroke. Expression of circRNA_102046 was detected in the cytoplasma of hNSCs. Then OGD/R cell model was established, where the levels of circRNA_102046 was significantly up-regulated. Furthermore, knockdown of circRNA_102046 was able to enhance the proliferation and differentiation of OGD/R hNSCs. In further downstream molecular studies, the results indicated that circRNA_102046 could participate in the occurrence and development of ischemic stroke through targeting miR-493-5p. In addition, ROCK1 was identified as the putative target of miR-493-5p, and circRNA_102046 regulates the proliferation and differentiation of hNSCs via the miR-493-5p/ROCK1 signaling. More importantly, the infarct volumes of MCAO mice were remarkably reduced after the treatment with sh-circRNA_102046, which also up- and down-regulate the expression of miR-493-5p and ROCK1, respectively. Elucidating this novel pathway provides a theoretical basis for the development of new diagnostic approach and targeted treatment for ischemic stroke.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This project was funded by Natural Science Foundation of Chongqing (Grant No. cstc2020jcyj-msxmX0358).

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Authors and Affiliations

  1. Department of General Medicine, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China

    Wentao He & Yuanyuan Cheng

  2. Department of Neurology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China

    Yujie Lai

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CY designed the study, and all authors carried out the experiments and data analysis. All authors drafted the manuscript and approved the final version of the paper.

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Correspondence to Yuanyuan Cheng.

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This study was approved by the Ethics Committee of the third affiliated hospital of Chongqing Medical University (Chongqing, China).

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He, W., Cheng, Y. & Lai, Y. CircRNA_102046 Affects the Occurrence and Development of Ischemic Stroke by Regulating the miR-493-5p/ROCK1 Signaling. Cardiovasc Toxicol 24, 280–290 (2024). https://doi.org/10.1007/s12012-024-09831-y

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