Role of N6-methyladenosine modification in pathogenesis of ischemic stroke

ABSTRACT

Introduction

N6-Methyladenosine (m6A), the most common and reversible mRNA modification, has attracted considerable attention recently, and accumulating evidence indicates it has an important role in the progression of ischemic stroke (IS).

Areas covered

We first reviewed m6A methylation modification enzymes, including m6A methyltransferases (METTL3, METTL14, and WTAP), demethylases (FTO and ALKBH5), m6A-binding proteins (YTH domain containing 1/2 [YTHDC1/2], YTHDF1/2/3, and insulin like growth factor 2 mRNA binding protein 1/2/3 [IGF2BP1/2/3]), and their-related functions. An alteration in the m6A methylation profile of IS has been reported and m6A is differentially expressed in IS. Thus, we then focused on the underlying mechanism of m6A methylation in IS and the involvement of atherosclerosis (AS), cerebral ischemia/reperfusion (IR) injury, inflammation, oxidative stress, and apoptosis. Furthermore, we also elucidated the effect of m6A-associated single-nucleotide polymorphisms (SNPs) on stroke and uncovered new causal variants for IS. The clinical application of m6A targeting drugs is still in its infancy and will be available in the future.

Expert opinion

Collectively, the information in the present review is a summary of the latest developments in m6A modification and highlights the mechanisms underlying IS pathogenesis, which may provide novel insights into the mechanisms and therapeutic targets for IS.

KEYWORDS:

• Ischemic stroke
• m6A
• prognosis
• diagnosis
• therapeutic

Article highlights

• This article focusses on the underlying mechanism of m6A methylation in the ischemic stroke from the aspects of atherosclerosis, cerebral ischemia reperfusion injury, inflammation, apoptosis and oxidative stress.

• This article also elucidated the effect of m6A-associated SNPs on stroke and uncovered new causal variants for IS.

• Collectively, the present review summarized the latest development regarding m6A modification and IS, which may provide novel insights into the role of m6A modification in pathogenesis of IS.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This study was supported by Natural Science Foundation of Liaoning province of China (2019-MS-364) and the National Natural Science Foundation of China (81501006).