Evidence map›Paper›PMID 38803048›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

USP25 Elevates SHLD2-Mediated DNA Double-Strand Break Repair and Regulates Chemoresponse in Cancer.

Yunhui Li, Lei Li, Xinshu Wang, Fei Zhao, Yuntong Yang, Yujuan Zhou, Jiyuan Zhang, Li Wang, Zeshan Jiang, Yuanyuan Zhang and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. USP25 inhibition ameliorates Parkinson's disease by restoring mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. 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

21 authors.

Yunhui LiMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Lei LiMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Xinshu WangMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Fei ZhaoCollege of Biology, Hunan University, Changsha, 410082, China.
Yuntong YangMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Yujuan ZhouMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Jiyuan ZhangMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Li WangMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Zeshan JiangMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Yuanyuan ZhangDepartment of General Surgery and Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Yuping ChenCancer Center, Tongji University School of Medicine, Shanghai, 200331, China.
Chenming WuMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Ke LiState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Tingting ZhangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Ping WangTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Shanghai, 200072, China.
Zhiyong MaoShanghai Key Laboratory of Maternal-Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, Tongji University School of Medicine, Shanghai, 200040, China.
Weiguo ZhuInternational Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen, 518037, China.
Xingzhi XuThe Sixth Affiliated Hospital of Shenzhen University, Guangdong Key Laboratory for Genome Stability and Disease Prevention and Carson International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University School of Medicine, Shenzhen, 518055, China.
Shikang LiangSchool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, 999077, Hong Kong.
Zhenkun LouDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Jian YuanMedical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.ORCID 0000-0002-2801-8849

Funding

Fundamental Research Funds for the Central Universities 22120230228Fundamental Research Funds for the Central Universities 22120240382National Key Research and Development Plan 2022YFA1302803National Natural Science Foundation of China 32070713National Natural Science Foundation of China 32090032National Natural Science Foundation of China 81802754National Natural Science Foundation of China 81872298National Natural Science Foundation of China 82225035Science and Technology Commission of Shanghai Municipality 22XD1422300Shanghai Municipal Health Bureau 2022XD053
6 · The paper itself

Abstract

DNA damage plays a significant role in the tumorigenesis and progression of the disease. Abnormal DNA repair affects the therapy and prognosis of cancer. In this study, it is demonstrated that the deubiquitinase USP25 promotes non-homologous end joining (NHEJ), which in turn contributes to chemoresistance in cancer. It is shown that USP25 deubiquitinates SHLD2 at the K64 site, which enhances its binding with REV7 and promotes NHEJ. Furthermore, USP25 deficiency impairs NHEJ-mediated DNA repair and reduces class switch recombination (CSR) in USP25-deficient mice. USP25 is overexpressed in a subset of colon cancers. Depletion of USP25 sensitizes colon cancer cells to IR, 5-Fu, and cisplatin. TRIM25 is also identified, an E3 ligase, as the enzyme responsible for degrading USP25. Downregulation of TRIM25 leads to an increase in USP25 levels, which in turn induces chemoresistance in colon cancer cells. Finally, a peptide that disrupts the USP25-SHLD2 interaction is successfully identified, impairing NHEJ and increasing sensitivity to chemotherapy in PDX model. Overall, these findings reveal USP25 as a critical effector of SHLD2 in regulating the NHEJ repair pathway and suggest its potential as a therapeutic target for cancer therapy.

Indexed as

DNA Breaks, Double-StrandedUbiquitin ThiolesteraseAnimalsCell Line, TumorColonic NeoplasmsDisease Models, AnimalDNA-Binding ProteinsDNA End-Joining RepairDNA RepairDrug Resistance, NeoplasmHumansMiceTranscription FactorsTripartite Motif ProteinsUbiquitin-Protein LigasesDNA-Binding ProteinsTranscription FactorsTRIM25 protein, humanTripartite Motif ProteinsUbiquitin-Protein LigasesUbiquitin ThiolesteraseUSP25 protein, humancancer therapydeubiquitinase USP25DNA repair pathwayspeptidesSHLD2

Identifiers

PMID38803048
PMCPMC11267380

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.