Evidence mapPaperPMID 42550296Full record

ArticleMolecular biology reports2026

METTL3-dependent m⁶A maturation of miR-140-3p contributes to hippocampal neuronal apoptosis through the OTX2/Wnt/β-catenin axis under chronic stress.

Yuanxiang Zhang, Xin Du, Mengxue Fu, Haitao Hu, Juan Lu, Tongshuai Pan, Lili Yuan, Yigao Wu, Jiucui Tong

Abstract read
In one paragraph

Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yuanxiang Zhang *School of Pharmacy, Wannan Medical University, Wuhu, 241002, China.
Xin Du *School of Pharmacy, Wannan Medical University, Wuhu, 241002, China.
Mengxue FuSchool of Pharmacy, Wannan Medical University, Wuhu, 241002, China.
Haitao HuSchool of Pharmacy, Wannan Medical University, Wuhu, 241002, China.
Juan LuSchool of Pharmacy, Wannan Medical University, Wuhu, 241002, China.
Tongshuai PanSchool of Pharmacy, Wannan Medical University, Wuhu, 241002, China.
Lili YuanDepartment of Medical Psychology, The First Affiliated Hospital of Wannan Medical University, Wuhu, 241001, China.
Yigao WuDepartment of Medical Psychology, The First Affiliated Hospital of Wannan Medical University, Wuhu, 241001, China. wuyigao2000@126.com.
Jiucui TongSchool of Pharmacy, Wannan Medical University, Wuhu, 241002, China. tongjiucui@wnmc.edu.cn.

Funding

the Major Humanities and Social Sciences Project of Universities in Anhui Province No. 2025AHGXSK20032the Major Natural Science Project of Universities in Anhui Province No. 2024AH040248Wannan Medical University Horizontal Research Project No. H202503
6 · The paper itself

Abstract

backgroundChronic stress contributes to hippocampal neuronal apoptosis and neural circuit dysfunction in major depressive disorder (MDD), but the epitranscriptomic mechanisms regulating stress-responsive microRNAs remain unclear. This study investigated whether methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification promotes miR-140-3p maturation and neuronal apoptosis through the OTX2/Wnt/β-catenin axis under chronic stress. METHODS AND

resultsA chronic unpredictable mild stress rat model and a corticosterone-induced primary hippocampal neuron injury model were established. Behavioral assays, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, flow cytometry, western blotting, qRT-PCR, proteomic and transcriptomic analyses, methylated RNA immunoprecipitation (MeRIP), DiGeorge syndrome critical region gene 8 (DGCR8) RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were performed. Serum miR-140-3p expression was also assessed in patients with MDD and healthy controls. miR-140-3p was upregulated in the hippocampus of stressed rats and in the serum of patients with MDD. Hippocampal miR-140-3p knockdown alleviated depressive-like behaviors and reduced neuronal apoptosis, whereas miR-140-3p inhibition protected primary hippocampal neurons from corticosterone-induced apoptosis. Mechanistically, chronic stress increased METTL3 expression and global m6A levels. METTL3 enhanced m6A modification of pri-miR-140-3p, promoted DGCR8-dependent processing, and increased mature miR-140-3p expression. miR-140-3p directly targeted OTX2 and modulated Wnt/β-catenin signaling, while OTX2 silencing attenuated the antiapoptotic effect of miR-140-3p inhibition.

conclusionsMETTL3-dependent m6A maturation of miR-140-3p may contribute to stress-induced hippocampal neuronal apoptosis through the OTX2/Wnt/β-catenin axis, providing potential molecular targets for further investigation in MDD.

Indexed as

HippocampusMethyltransferasesMicroRNAsOtx Transcription FactorsStress, PsychologicalAdenosineAnimalsApoptosisbeta CateninEpitranscriptomeHumansMaleNeuronsRatsRats, Sprague-DawleyRNA MethylationAdenosinebeta CateninMethyltransferasesMicroRNAsN-methyladenosineOtx Transcription FactorsDepressionMETTL3miR-140-3pN 6-methyladenosineNeuronal apoptosisOTX2Wnt/β-catenin signaling pathway

Identifiers

PMID42550296
PMCPMC13437767

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.