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Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2

Authors Wu Y, Gao Z, Zhang J

Received 8 July 2020

Accepted for publication 14 September 2020

Published 4 November 2020 Volume 2020:16 Pages 2633—2647


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yuping Ning

Yunxia Wu, Zhiqiang Gao, Jiang Zhang

Department of Neurology, Linyi Central Hospital, Linyi, Shandong 276400, People’s Republic of China

Correspondence: Jiang Zhang Department of Neurology, Linyi Central Hospital, No. 17, Jiankang Road, Yishui County, Linyi 276400, Shandong, People’s Republic of China
Tel/Fax +86-0539-22260223

Background: It has been documented that microRNAs (miRs) assume a pivotal role in the development of ischemic stroke (IS). However, it remains poorly identified about the role of miR-122 in IS. Herein, this study was intended to explore the mechanism of E2F1-orchestrated miR-122 in IS.
Patients and Methods: E2F1, miR-122, and SPRY2 expression in serum from patients with IS and oxygen-glucose deprivation (OGD)-treated N2a cells was detected by RT-qPCR. After gain- and loss-of-function approaches in OGD-induced N2a cells, GAFP staining, flow cytometry, and Western blot analysis were adopted to assess neuronal viability, cell cycle and apoptosis, and expression of apoptosis- and autophagy-related proteins, respectively. Meanwhile, mice with IS were induced, in which E2F1, miR-122, and SPRY2 were overexpressed, followed by evaluation of neurological deficit and cerebral infarction area. The MAPK pathway activity in tissues of mice and cells was determined.
Results: miR-122 was down-regulated, and E2F1 and SPRY2 were up-regulated in IS patients and OGD-induced N2a cells. E2F1 inhibited miR-122 transcription, while miR-122 targeted SPRY2. Overexpression (OE) of miR-122 or down-regulation of E2F1 or SPRY2 increased viability, but decreased apoptosis, cell cycle arrest, and autophagy in OGD-induced N2a cells. In IS mice, the neurological deficit score and cerebral infarction area were elevated, which was aggravated by up-regulating E2F1 or SPRY2 but attenuated by overexpressing miR-122. E2F1/miR-122/SPRY2 axis mediated the MAPK pathway in vivo and in vitro.
Conclusion: Collectively, E2F1 reduced miR-122 transcription to up-regulate SPRY2, which inactivated MAPK pathway and promoted neurological deficit in IS.

Keywords: ischemic stroke; IS, E2F1, microRNA-122, SPRY2, MAPK pathway, neurological injury

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