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lncfos/miR-212-5p/CASP7 Axis-Regulated miR-212-5p Protects the Brain Against Ischemic Damage

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A Correction to this article was published on 23 February 2023

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Abstract

miR-212-5p has been reported to be involved in many biological processes. However, the role of miR-212-5p in ischemic stroke remains unclear. This study explored the biological role and potential mechanism of miR-212-5p in ischemic stroke by investigating the lncfos/miR-212-5p/CASP7 axis. A total of 32 patients with ischemic stroke and 32 age- and sex-matched healthy controls (HCs) were enrolled in this study. In addition, 336 rats were used in this study. The rats were subjected to middle cerebral artery occlusion (MCAO) and intracerebroventricular injection of a microRNA (miRNA) agomir, a miRNA antagomir, a short hairpin RNA (shRNA) lentiviral vector, or a negative control. The neurological deficit score was calculated; the infarct volume was measured; histopathological assays were performed; the neuronal apoptosis rate was determined; and the lncfos, miR-212-5p, and CASP7 expression levels in the peri-infarct area were assessed. In this study, we found that the expression level of miR-212-5p was significantly downregulated in the peri-infarct area and blood of the MCAO model rats and the blood of patients with ischemic stroke. A double-luciferase experiment showed that CASP7 was a direct target gene of miR-212-5p and that miR-212-5p was a target miRNA of lncfos. Lateral ventricular injection of the miR-212-5p agomir effectively inhibited the apoptosis induced by ischemic brain damage, reduced the infarct volume, attenuated the neurological deficit symptoms, and downregulated the expression of CASP7 in the peri-infarct area of the MCAO model rats. Suppressing lncfos with sh-fos led to the upregulated expression of miR-212-5p and played a neuroprotective role in the rat MCAO models. We concluded that miR-212-5p plays a neuroprotective role in ischemic stroke and that its function is regulated by the lncfos/miR-212-5p/CASP7 axis. Moreover, miR-212-5p may be a potential biomarker and therapeutic target for ischemic stroke.

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Acknowledgements

We are grateful to the patients and their family members for their participation.

Funding

The present study was supported by the National Key R&D Program of China (2017YFC1307500, 2017YFC1307503) and by grants from the National Natural Science Foundation of China (no. 81160168, 81460321, and 81660354).

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  1. Department of Neurology, Guangxi Academy of Medical Sciences, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China

    Shenghua Li

  2. Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China

    Xiang Qu, Zhenxiu Qin, Jinggui Gao, Jinpin Li & Jingli Liu

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Contributions

JL-L and SH-L designed the study. SH-L, XQ, ZX-Q, and JG-G performed the experiments. SH-L, JL-L, and JP-L analyzed the results together. SH-L wrote the article. All authors have approved the final submitted manuscript.

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Correspondence to Jingli Liu.

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This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of China Medical University (NO.2018-KY-E-063) and the Animal Care and Use Committee of Guangxi Medical University (No. 201801070).

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Li, S., Qu, X., Qin, Z. et al. lncfos/miR-212-5p/CASP7 Axis-Regulated miR-212-5p Protects the Brain Against Ischemic Damage. Mol Neurobiol 60, 2767–2785 (2023). https://doi.org/10.1007/s12035-023-03216-y

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