ArticleCancer cell international2019
OTU deubiquitinase 4 is silenced and radiosensitizes non-small cell lung cancer cells via inhibiting DNA repair.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- OTUD4 stabilizes CYLD and counteracts BCL3 K63-linked polyubiquitination to suppress melanoma progression.Cell death & disease · 2026Article
- OTUD4 regulates pancreatic cancer progression via Hippo/YAP axis.Neoplasia (New York, N.Y.) · 2026Article
- Glycolytic Reprogramming Mediated by the OTUD4-FXR1-HIF1A Axis Drives Gastric Cancer Progression.International journal of biological sciences · 2026Article
- OTUD4 Inhibits Prostate Cancer by Deubiquitinating MYH9.Oncology research · 2026Article
- Geno-guided targeting of ferroptosis: a multi-layered network to overcome radioresistance in lung cancer.Frontiers in cell and developmental biology · 2026Review
- The deubiquitinase OTUD1 orchestrates cisplatin chemosensitivity of non-small cell lung cancer through destabilizing RAD23B/XPC.Oncogene · 2025Article
- OTUD4 suppresses colorectal cancer progression through deubiquitinating p53.Discover oncology · 2025Article
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- Mechanisms Underlying Radioresistance and Reversal Strategies in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- Review
- Deubiquitinating enzyme OTUD4 stabilizes RBM47 to induce ATF3 transcription: a novel mechanism underlying the restrained malignant properties of ccRCC cells.Apoptosis : an international journal on programmed cell death · 2024Article
- MicroRNA-384 radiosensitizes human non-small cell lung cancer by impairing DNA damage response and repair signaling, which is inhibited by NF-κB.Cancer biology & medicine · 2024Article
- OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway.Cell death & disease · 2024Article
- CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation.Cell death & disease · 2023Article
- Long noncoding RNA LINC00173 induces radioresistance in nasopharyngeal carcinoma via inhibiting CHK2/P53 pathway.Cancer gene therapy · 2023Article
- Prospects and feasibility of synergistic therapy with radiotherapy, immunotherapy, and DNA methyltransferase inhibitors in non-small cell lung cancer.Frontiers in immunology · 2023Review
- Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRadiotherapy is becoming one major therapeutics for non-small cell lung cancer (NSCLC). Identifying novel radiosensitizers will greatly increase the efficacy of radiotherapy and benefit more patients. OTU deubiquitinase 4 (OTUD4) has been reported involved in DNA damage repair pathways and could be a potential target for chemotherapy therapy. This study aimed to investigate the roles of OTUD4 in regulation of radiosensitivity of NSCLC via modulating DNA repair.
methodsThe expression of OTUD4, γ-H2Ax and ATM/CHK2/p53 pathway-related signaling molecules were detected by Western blotting and QRT-PCR. The methylation of OTUD4 promoter was investigated by 5-aza-deoxycytidine treatment, methylation-specific PCR and bisulfite genomic sequencing assays. Radiosensitivity was assessed by the clonogenic formation assay. Cell cycle, cell apoptosis were analyzed by flow cytometry. DNA damage and repair were determined by comet assay, γ-H2Ax foci staining and flow cytometry.
resultsOTUD4 is dramatically downregulated in NSCLC and its downregulation significantly correlates with poor prognosis of NSCLC patients. Promoter hypermethylation is responsible for the loss of OTUD4 expression in NSCLC cells. Overexpression of OTUD4 increases radiosensitivity of NSCLC cells exhibiting as impaired clonogenic formation ability, enhanced cell cycle arrest and increased cell apoptosis. Moreover, molecular mechanism study reveals that OTUD4 radiosensitizs NSCLC cells via ATM/CHK2/P53 signaling and inhibiting homology-directed repair of DNA double strand breaks induced by ionizing radiation.
conclusionsThis study uncovers a tumor-suppressing role of OTUD4 and that OTUD4 is a potential radiosensitizer for NSCLC.
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