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The Role and Diagnostic Efficacy of the METTL14/GADD45B m<sup>6</sup>A Methylation/BDNF Regulatory Axis in Acute Ischemic Stroke.

Overview

Authors: Jin-ying Lai1, Jun-hua Lu2, Meng-yue Li1, Bei-bei Li1, Bao-yun Jin1, Jiang-jie Hao1, Ying Zhao3, Ying Lin3, Li-qiu Ma3, Ren Liu1, Shu-fan Zhang1, Hong-jun Guan1
ORCID iDs: Jin-ying Lai, Jun-hua Lu, Meng-yue Li, Bei-bei Li, Bao-yun Jin, Jiang-jie Hao, Ying Zhao, Ying Lin, Li-qiu Ma, Ren Liu, Shu-fan Zhang, Hong-jun Guan
  1. Department of Public Health, Mudanjiang Medical University, Mudanjiang, China
  2. Department of Nursing, Mudanjiang Medical University, Mudanjiang, China
  3. Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
Institutions: Mudanjiang Medical University (China)
Journal: Cellular and molecular neurobiology, volume 46, issue 1, article 119
Dates: received 10 November 2025; accepted 4 March 2026; published online 16 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1007/s10571-026-01710-0 · PMID 41989611 · PMCID PMC13385536 · OpenAlex W7154638537
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: human (organism), stroke (population), clinical / translational (subfield)
Methods: Statistics, Machine learning, Connectivity
Keywords: Acute ischemic stroke, N6-methyladenosine (m6A) methylation, Diagnosis, METTL14, GADD45B, BDNF
MeSH: Adenosine*, Antigens, Differentiation*, Brain-Derived Neurotrophic Factor*, Ischemic Stroke*, Methyltransferases*, Aged, Biomarkers, Female, GADD45 Proteins, Human Umbilical Vein Endothelial Cells, Humans, Male, Middle Aged, RNA Methylation (* major topic)
Topic: RNA modifications and cancer (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Natural Science Foundation of Heilongjiang Province (PL2025H232)
Citations: not cited yet (Europe PMC); 57 references in the paper
Research resources: RRID:AB_2769854, RRID:AB_2770239

Abstract

Despite advances in acute ischemic stroke (AIS) research, identifying reliable biomarkers and regulatory mechanisms remains challenging. We first identified AIS-related genes via extensive literature review, retrieved dataset GSE16561 from the Gene Expression Omnibus (GEO, https://ncbi.nlm.nih.gov/geo/), and performed differential/enrichment analyses. Bioinformatics verified N6-methyladenosine (m6A) sites in target genes, focusing on the methyltransferase-like protein 14 (METTL14)/growth arrest and DNA damage-inducible β (GADD45B) m6A methylation/brain-derived neurotrophic factor (BDNF) axis. Peripheral blood samples, biochemical indicators, and demographic data were collected from Hongqi Hospital Affiliated to Mudanjiang Medical University. Human umbilical vein endothelial cells (HUVECs) underwent transfection and oxygen-glucose deprivation (OGD). METTL14, GADD45B, and BDNF were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR); BDNF protein by enzyme-linked immunosorbent assay (ELISA); global RNA m6A by Dot Blot; and GADD45B m6A by methylated RNA immunoprecipitation-quantitative polymerase chain reaction (MeRIP-RT-qPCR). Differential, diagnostic efficacy, logistic regression analyses, and nomogram validation were conducted. AIS patients showed increased METTL14, decreased GADD45B/BDNF, and increased levels of global m6A RNA and GADD45B m6A mRNA (P < 0.05). Receiver operating characteristic (ROC) analysis confirmed the three genes’ good diagnostic efficacy. The nomogram integrating these genes, globulin (GLOB), diabetes, high-density lipoprotein cholesterol (HDL-C), and hypertension performed excellently. This study highlights METTL14, GADD45B, and BDNF as key AIS biomarkers; METTL14 may indirectly regulate BDNF via GADD45B m6A methylation, providing potential therapeutic targets and novel mechanistic insights.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10571-026-01710-0.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 6 keywords, 14 MeSH terms, 1 funder, 57 references, 2 RRIDs.

Cite

This paper

Lai, J.-y., Lu, J.-h., Li, M.-y., Li, B.-b., Jin, B.-y., Hao, J.-j., Zhao, Y., Lin, Y., Ma, L.-q., Liu, R., Zhang, S.-f., & Guan, H.-j. (2026). The Role and Diagnostic Efficacy of the METTL14/GADD45B m&lt;sup&gt;6&lt;/sup&gt;A Methylation/BDNF Regulatory Axis in Acute Ischemic Stroke. Cellular and molecular neurobiology, 46(1), 119. https://doi.org/10.1007/s10571-026-01710-0

BibTeX

@article{lai2026role,
author = {Lai, Jin-ying and Lu, Jun-hua and Li, Meng-yue and Li, Bei-bei and Jin, Bao-yun and Hao, Jiang-jie and Zhao, Ying and Lin, Ying and Ma, Li-qiu and Liu, Ren and Zhang, Shu-fan and Guan, Hong-jun},
title = {{The Role and Diagnostic Efficacy of the METTL14/GADD45B m\&lt;sup\&gt;6\&lt;/sup\&gt;A Methylation/BDNF Regulatory Axis in Acute Ischemic Stroke}},
journal = {Cellular and molecular neurobiology},
year = {2026},
month = apr,
volume = {46},
number = {1},
pages = {119},
publisher = {Springer},
issn = {0272-4340},
doi = {10.1007/s10571-026-01710-0},
url = {https://doi.org/10.1007/s10571-026-01710-0},
pmid = {41989611},
pmcid = {PMC13385536}
}

RIS

TY - JOUR
AU - Lai, Jin-ying
AU - Lu, Jun-hua
AU - Li, Meng-yue
AU - Li, Bei-bei
AU - Jin, Bao-yun
AU - Hao, Jiang-jie
AU - Zhao, Ying
AU - Lin, Ying
AU - Ma, Li-qiu
AU - Liu, Ren
AU - Zhang, Shu-fan
AU - Guan, Hong-jun
TI - The Role and Diagnostic Efficacy of the METTL14/GADD45B m&lt;sup&gt;6&lt;/sup&gt;A Methylation/BDNF Regulatory Axis in Acute Ischemic Stroke
T2 - Cellular and molecular neurobiology
J2 - Cell Mol Neurobiol
PY - 2026
DA - 2026/04/16
VL - 46
IS - 1
SP - 119
SN - 0272-4340
PB - Springer
DO - 10.1007/s10571-026-01710-0
UR - https://doi.org/10.1007/s10571-026-01710-0
LA - en
ER -

CSL-JSON

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