Evidence mapPaperPMID 42378628Full record

ArticleMolecular carcinogenesis2026

Ubiquitin Specific Peptidase 48 Deubiquitinates METTL3 to Modulate Ferroptosis in Gastric Cancer Cells.

Yi-Lin Xie, Tian-Xia Lei, Yong-Sheng Zheng, Ze-Lin Xu, Hai-Xing Wang

Abstract read
In one paragraph

Article in Molecular carcinogenesis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Article
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

5 authors.

Yi-Lin XieDepartment of Endoscopy Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Tian-Xia LeiDepartment of Endoscopy Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Yong-Sheng ZhengDepartment of Endoscopy Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Ze-Lin XuDepartment of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Hai-Xing WangDepartment of Endoscopy Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Funding

Xiamen's Guiding Project for Medical and Health Care 3502Z20244ZD1006
6 · The paper itself

Abstract

Ferroptosis, an iron-dependent cell death, is a promising target in gastric cancer. METTL3, an m6A RNA methyltransferase, drives tumor progression, but its role in ferroptosis regulation and the involved deubiquitinating enzymes (DUBs) remain unclear. Here, we demonstrated that METTL3 expression heterogeneity in different gastric cancer cells, identified functional role of METTL3 in modulating ferroptosis sensitivity. In MKN-7 and GCIY cells, forced METTL3 overexpression conferred resistance to ferroptotic stress by driven GPX4 and FTH1 expression, and inhibiting oxidative stress accumulation. Conversely, METTL3 depletion sensitized cells to ferroptosis, and promoted ferroptotic oxidative damage. Through a comprehensive screening of deubiquitinases, we identified ubiquitin specific peptidase 48 (USP48) as a critical stabilizer of METTL3 protein. Functional assays revealed that USP48 mimics METTL3's protective role against ferroptosis, while METTL3 overexpression rescued the ferroptosis sensitivity caused by USP48 knockdown. Mechanistically, this USP48-METTL3 axis regulated key ferroptosis markers including GPX4, FTH1, lipid peroxidation, iron accumulation, and reactive oxygen species (ROS) levels. Our findings reveal a novel regulatory pathway by which USP48 controls ferroptosis sensibility in gastric cancer cell via METTL3 stabilization. This crosstalk between the ubiquitin-proteasome system and m6A transferases highlights the USP48-METTL3 axis as a promising target to sensitize gastric cancer cells to ferroptosis-inducing therapy.

Indexed as

FerroptosisMethyltransferasesStomach NeoplasmsUbiquitin-Specific ProteasesCell Line, TumorGene Expression Regulation, NeoplasticHumansOxidative StressReactive Oxygen SpeciesUbiquitinationMethyltransferasesMETTL3 protein, humanReactive Oxygen SpeciesUbiquitin-Specific Proteasesdeubiquitinating enzymesFerroptosisGastric cancerMETTL3USP48

Identifiers

PMID42378628
PMCPMC13465995

What Socratic holds

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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.