Evidence map›Paper›PMID 41413718›Full record

ArticleCommunications biology2025

TRIM21 promotes K63-linked ubiquitination of ALKBH5 and suppresses cuproptosis via down-regulation of LIAS in esophageal squamous cell carcinoma.

Anqi Feng, Lingnan He, Zhaoxing Li, Zeyu Wang, Mingchuang Sun, Ziying Zhao, Zehua Zhang, Kang Fang, Hao Wu, Xiaoyuan Wang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. 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

15 authors.

Anqi Feng *Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.ORCID http://orcid.org/0000-0002-9306-0189
Lingnan He *Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Zhaoxing Li *Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Zeyu WangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Mingchuang SunEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Ziying ZhaoEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Zehua ZhangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Kang FangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Hao WuEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Xiaoyuan WangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Shihan ZhangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Zhukai ChenEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Li ZhangDepartment of Pathology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Tao ChenEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. chentao@tongji.edu.cn.ORCID http://orcid.org/0000-0002-8016-9732
Meidong XuEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. 1800512@tongji.edu.cn.ORCID http://orcid.org/0000-0002-7219-5826

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82072684National Natural Science Foundation of China (National Science Foundation of China) 82073224National Natural Science Foundation of China (National Science Foundation of China) 82203341National Natural Science Foundation of China (National Science Foundation of China) 82372921
6 · The paper itself

Abstract

Cuproptosis is a newly discovered programmed cell death regulated by lipoic acid synthase (LIAS) in cancer cells. However, its functions in Esophageal squamous cell carcinoma (ESCC) and the underlying mechanism remains unclear. Here, we show that in human ESCC cells, TRIM21 facilitates the K63-linked ubiquitination dependent translocation of ALKBH5 from cytosol to nucleus and augments its m6A demethylase activity. LIAS mRNA was demethylated by ALKBH5, and then further identified by reader IGF2BP3, which comprehensively caused the lower expression of LIAS. Moreover, O-GlcNAc transferase OGT facilitated TRIM21-mediated K63-ubiquitination of ALKBH5. Combined treatment with an OGT inhibitor OSMI-1 and copper ionophore elesclomol eliminates tumor growth and remarkably enhances the sensitivity of tumor cells to cisplatin. Together, our study identifies TRIM21 Ubiquitinated-ALKBH5 as a critical gatekeeper to restrict cuproptosis, and such mechanism may contribute to tumor development and drug resistance in ESCC.

Indexed as

AlkB Homolog 5, RNA DemethylaseEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaRibonucleoproteinsAnimalsCell Line, TumorDown-RegulationGene Expression Regulation, NeoplasticHumansMiceSS-A AntigenUbiquitinationALKBH5 protein, humanAlkB Homolog 5, RNA DemethylaseRibonucleoproteinsSS-A Antigen

Identifiers

PMID41413718
PMCPMC12715190

What OpenQuestion holds

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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 OpenQuestion graph.