Evidence map›Paper›PMID 40181152›Full record

ArticleOncogene2025

Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma.

Deng-Yong Zhang, Yan Zhu, Shuo-Shuo Ma, Chen-Yang Xu, Zhong-Lin Wang, Hui Wang, Si-Hua Liu, Jin Shang, Xiao-Lun Huang, Prit Benny Malgulwar and 3 more

Abstract read
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In one paragraph

Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

13 authors.

Deng-Yong Zhang *Department of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Yan Zhu *College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.
Shuo-Shuo Ma *Department of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Chen-Yang Xu *Medical College, Shaoxing University, Shaoxing, China.
Zhong-Lin WangSchool of Public Policy & Management, Tsinghua University, Beijing, China.
Hui WangMedical College, Shaoxing University, Shaoxing, China.
Si-Hua LiuDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Jin ShangLiver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Xiao-Lun HuangLiver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Prit Benny MalgulwarCollege of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.
Fang-Fang ChenDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Wei-Ying ZhaoMedical College, Shaoxing University, Shaoxing, China. zhaoweiying@usx.edu.cn.
Zheng LuDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China. luzhengdr@bbmc.edu.cn.ORCID http://orcid.org/0000-0002-8248-3426

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholangiocarcinoma (CCA) is a highly heterogeneous group of malignant tumors with different molecular etiologies and clinical manifestations. Post-translational modifications (PTM) such as ubiquitination and phosphorylation are widely involved in the progression of CCA. Our aim was to elucidate the effect of the deubiquitinating enzyme OTU domain-containing protein 3 (OTUD3) on the molecular pathogenesis of CAA. OTUD3 and ARID3A exhibit direct binding interactions and cytosolic substructural co-localization in CCA cells.OTUD3 specifically removes the ARID3A proteins K240 and K329 OTUD3 specifically removes the ubiquitinated chains at K240 and K329 of ARID3A protein, thereby enhancing ARID3A stability. OTUD3 promotes CCA proliferation and metastasis in vivo and in vitro by interacting with ARID3A.GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein. The expression of OTUD3 and ARID3A in CCA tissues is highly correlated, and the high expression of both proteins is closely related to the poor prognosis of patients. In conclusion, GSK3β phosphorylates OTUD3, enhances its binding ability to ARID3A, and ultimately inhibits the ubiquitination degradation of ARID3A, which promotes the progression of CCA. The GSK3β-OTUD3-ARID3A signaling pathway has been demonstrated for the first time in the progression of CCA.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaDNA-Binding ProteinsTranscription FactorsAnimalsCell Line, TumorCell ProliferationDisease ProgressionFemaleGene Expression Regulation, NeoplasticGlycogen Synthase Kinase 3 betaHumansMaleMicePhosphorylationUbiquitinationARID3A protein, humanDNA-Binding ProteinsGlycogen Synthase Kinase 3 betaTranscription Factors

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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 OpenQuestion graph.