Int J Biol Sci 2021; 17(13):3659-3671. doi:10.7150/ijbs.61399 This issue

Research Paper

Downregulation of miR-23b by transcription factor c-Myc alleviates ischemic brain injury by upregulating Nrf2

Rui Xin1,2, Danhua Qu1,3, Shuang Su4, Bin Zhao1,5, Dawei Chen1,6✉

1. Jilin University, Changchun 130000, P. R. China.
2. Department of Radiology, the Second Hospital of Jilin University, Changchun 130000, P. R. China.
3. Department of Respiratory and Critical Diseases, the Second Hospital of Jilin University, Changchun 130000, P. R. China.
4. Sinopec Research Institute of Safety Engineering, Qingdao 266000, P. R. China.
5. Department of Neurosurgery, the Second Hospital of Jilin University, Changchun 130000, P. R. China.
6. Department of Radiation Protection, School of Public Health, Jilin University, Changchun 130000, P. R. China.

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Citation:
Xin R, Qu D, Su S, Zhao B, Chen D. Downregulation of miR-23b by transcription factor c-Myc alleviates ischemic brain injury by upregulating Nrf2. Int J Biol Sci 2021; 17(13):3659-3671. doi:10.7150/ijbs.61399. Available from https://www.ijbs.com/v17p3659.htm

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Abstract

Graphic abstract

Ischemic brain injury (IBI) is a common acute cerebral vessel disease that occurs secondary to blockage in arteries, mainly characterized by insufficient blood supply to the brain. The transcription factor c-Myc in IBI continues to be implicated in numerous studies. This study was conducted with emphasis placed on the underlying mechanism of c-Myc in IBI. Clinical samples were collected from IBI patients. Middle cerebral artery occlusion (MCAO) was induced in mice by inserting a suture from the external carotid artery to the anterior cerebral artery through the internal carotid artery to mechanically block the blood supply at the origin of the middle cerebral artery, and cortical neurons from mice were exposed to oxygen glucose deprivation (OGD) conditions for IBI model in vitro construction. RT-qPCR was performed to determine microRNA-23b (miR-23b) expression. TUNEL staining and Western blot analysis was conducted to detect apoptosis. The regulatory relationship was analyzed by dual-luciferase reporter gene assay. After loss- and gain-of-function assays, triphenyltetrazolium chloride staining was carried out to detect the area of cerebral infarction, after which the spatial memory in mice was evaluated with Morris water maze test. As per our findings, miR-23b was upregulated in the serum of IBI patients and OGD-treated murine primary neurons. Silencing of miR-23b resulted in reduced OGD-induced neuronal apoptosis. miR-23b inversely targeted nuclear factor erythroid 2-related factor 2 (Nrf2) and c-Myc negatively regulated miR-23b expression. Overexpression of c-Myc and inhibition of miR-23b led to reduced neurological scores of infarction area, neuronal apoptosis, shortened platform arrival time and significantly increased the time spent on the platform quadrant and the times of crossing the platform in vivo. Collectively, downregulated miR-23b by c-Myc might alleviate IBI by upregulating Nrf2.

Keywords: Ischemic brain injury, c-Myc, microRNA-23b, Nuclear factor erythroid 2-related factor 2, Middle cerebral artery occlusion