Evidence map›Paper›PMID 40078091›Full record

ArticleClinical and translational medicine2025

PADI4 facilitates stem-like properties and cisplatin resistance through upregulating PRMT2/IDs family in oesophageal squamous cell carcinoma.

Zeyu Wang, Hao Wu, Zhaoxing Li, Zhukai Chen, Anqi Feng, Yuan Chu, Kang Fang, Zehua Zhang, Ziying Zhao, Zhuyun Leng and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. USP35 Acts as a Deubiquitinating Enzyme for ID3 to Promote Immune Escape in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Review
  4. Review
  5. Article
  6. 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.

Zeyu WangDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID 0000-0001-6264-634X
Hao WuDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhaoxing LiDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhukai ChenDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Anqi FengDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Yuan ChuDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Kang FangDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zehua ZhangDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Ziying ZhaoDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhuyun LengDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Shihan ZhangDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiaoyuan WangDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Lingnan HeDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Tao ChenDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Meidong XuDepartment of Gastroenterology, Endoscopy Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID 0000-0002-7219-5826

Funding

Fundamental Research Funds for the Central Universities 22120240371Fundamental Research Funds for the Central Universities 22120240372National Natural Science Foundation of China 82372921National Natural Science Foundation of China 82473094Outstanding Young Medical Talents and Outstanding Projects of Shanghai Municipal Health Commission 20224Z0016Pudong Health Committee of Shanghai 2024-PWXZ-007Pudong Health Committee of Shanghai 2025PDWSYCBJ-01Pudong Health Committee of Shanghai PWRq2024-10Pudong Health Committee of Shanghai PWZxq2022-06
6 · The paper itself

Abstract

backgroundOesophageal squamous cell carcinoma (OSCC) is a highly lethal cancer characterized by its aggressive nature and chemotherapy resistance. Peptidylarginine deiminase 4 (PADI4) regulates protein citrullination and is associated with various cancer developments. The role of PADI4 in OSCC progression and chemoresistance remains unexplored.

methodsThe protein interactions were conducted by immunoprecipitation assays. Quantitative real-time PCR and western blotting were utilized to quantifyexpression levels in cancer cells. The stem-like properties were assessed through spheroid growth assays and Cancer Stem Cells (CSCs) markers. Additionally, the resistance of cancer cells to cisplatin was evaluated using CCK8 assay.

resultsThis study shows that PADI4 promotes cellular stemness, contributing to the progression and chemoresistance of OSCC. Mechanistically, PADI4 facilitates the citrullination of protein arginine methyltransferase 2 (PRMT2), a process essential for the stabilization of PRMT2 expression and the enhancement of its function in promoting the transcription of IDs family (ID1 and ID2) via histone arginine methylation. This mechanism subsequently increases tumour stemness and contributes to the cisplatin resistance observed in OSCC. Mutations at the R312 site or inhibition by GSK484 can attenuate tumour stemness in OSCC, thereby reducing cisplatin resistance.

conclusionPADI4 promotes citrullination and stabilization of PRMT2, enhancing its function in upregulating ID1 and ID2 expression via histone arginine methylation, which increases stemness and contributes to cisplatin resistance in OSCC; this effect can be mitigated by R312 mutations or GSK484 inhibition, reducing stemness and cisplatin resistance. KEY POINTS: The role of citrullinization in cisplatin resistance of OSCC. PADI4 citrullinate of PRMT2 and stabilize PRMT2. PADI4 citrullinate of PRMT2 promoting the transcription of IDs family (ID1, ID2 and ID3) via histone arginine methylation. PADI4 citrullinated PRMT2 affected the combination of PRMT2 and USP7. PADI4 citrullinate of PRMT2 at R312 site. PADI4 inhibitor GSK484 can affect the stemness of OSCC and cisplatin resistance.

Indexed as

CisplatinDrug Resistance, NeoplasmEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaProtein-Arginine Deiminase Type 4Protein-Arginine N-MethyltransferasesCell Line, TumorHumansNeoplastic Stem CellsUp-RegulationCisplatinPADI4 protein, humanProtein-Arginine Deiminase Type 4Protein-Arginine N-MethyltransferasescisplatincitrullinationOSCCPADI4PRMT2

Identifiers

PMID40078091
PMCPMC11904308

What Socratic holds

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LicenceCC BY
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Registered trials

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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.