Open Access

ARTICLE

MELLT3 protects against cerebral ischemia-reperfusion (I/R) injury through up-regulation of m6A modification

by JING JIN^1,#, XINGHUA WANG^2,#, XIAOXIAO ZHENG³, JIAHUA LAN³, LI ZHENG³, YING CAI³, HUI CHEN⁴, HONGWEI WANG^5,*, LIFANG ZHENG^6,*

1 Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
2 Department of Neurology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, 430081, China
3 Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, China
4 Department of Animal Experimental Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 10003, China
5 Department of Anesthesiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, China
6 Department of Neurology, Yantian Hospital of Southern University of Science and Technology, Shenzhen, 518000, China

* Corresponding Authors: HONGWEI WANG. Email: ; LIFANG ZHENG. Email:
# These authors contributed to this work equally and should be regarded as co-first authors

BIOCELL 2023, 47(3), 619-626. https://doi.org/10.32604/biocell.2023.026016

Received 11 August 2022; Accepted 24 October 2022; Issue published 03 January 2023

Abstract

Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury (CIRI). The exact mechanisms underlying I/R injury are unclear. In this study, we aimed to determine the role of m⁶A-modified methylase complex methyltransferase-like 3 (METTL3) in cerebral ischemia-reperfusion (I/R) injury. We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytes-cerebellar (MA-C) and the brain of middle cerebral artery occlusion (MCAO) model mice. METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation, which increased with METTL3 over-expression. Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis, which was significantly reduced with METTL3 up-regulation. In an MCAO model, METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis, indicating that METTL3 OE treatment could ameliorate brain edema and injury. Thus, METTL3 could be used as a target to treat I/R injury.

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Keywords

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