ArticleCancer medicine2022
RAD18 confers radioresistance of esophagus squamous cell carcinoma through regulating p-DNA-PKcs.
Article in Cancer medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Progress for RAD18's mechanism in breast cancer radioresistant.Open life sciences · 2026Review
- Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control.International journal of pharmaceutics: X · 2025Review
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- RAD18 promotes cell malignant behaviors of esophageal squamous cell carcinoma by modulating ATM/STAT3/PD-L1.Chromosoma · 2025Article
- ADAR1 enhances tumor proliferation and radioresistance in non-small cell lung cancer by interacting with Rad18.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- MicroRNA-379-5p attenuates cancer stem cells and reduces cisplatin resistance in ovarian cancer by regulating RAD18/Polη axis.Cell death & disease · 2025Article
- USP9X-mediated REV1 deubiquitination promotes lung cancer radioresistance via the action of REV1 as a Rad18 molecular scaffold for cystathionine γ-lyase.Journal of biomedical science · 2024Article
- Structural basis for RAD18 regulation by MAGEA4 and its implications for RING ubiquitin ligase binding by MAGE family proteins.The EMBO journal · 2024Article
- The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.Biomedicines · 2023Review
- Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma.Molecular cancer · 2023Review
- RAD18 confers radioresistance of esophagus squamous cell carcinoma through regulating p-DNA-PKcs.Cancer medicine · 2022Article
- Biological Mechanisms to Reduce Radioresistance and Increase the Efficacy of Radiotherapy: State of the Art.International journal of molecular sciences · 2022Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRadiotherapy has recently become more common for the treatment of esophageal squamous cell carcinoma (ESCC). Radioresistance, on the other hand, continues to be a major issue because it interferes with the effectiveness of ESCC radiation. It has been demonstrated that RAD18, an E3 ubiquitin-protein ligase that regulates translesion DNA synthesis (TLS), is implicated in the regulation of genomic integrity and DNA damage response.
methodsIn the present study, immunohistochemical staining and western blotting were utilized to determine RAD18 expression in ESCC tissues and cells. ESCC cell proliferation was determined using a colony formation assay. Immunofluorescence staining, comet assay, and homologous recombination (HR)/non-homologous end-joining (NHEJ) assays were conducted to examine the effect of RAD18 on the DNA damage response in ESCC cells.
resultsWe found that high RAD18 expression was positively associated with a poorer prognosis in patients with ESCC who received radiotherapy. Downregulation of RAD18 expression significantly increased the sensitivity of ESCC cells to irradiation. Moreover, RAD18 knockdown prolonged the repair kinetics of γH2AX foci and resulted in longer comet tails. Furthermore, loss of RAD18 expression markedly decreased non-homologous end-joining (NHEJ) activity, but it did not affect homologous recombination (HR)-mediated double-strand break repair in ESCC cells. RAD18 upregulated p-DNA-dependent protein kinase complex (p-DNA-PKc) expression in vivo and in vitro.
conclusionsThese data indicated that RAD18 may regulate radioresistance by facilitating NHEJ via phosphorylation of DNA-PKcs in ESCC cells, providing a novel radiotherapy target for ESCC.
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