ArticleBMC cancer2017
XLF-mediated NHEJ activity in hepatocellular carcinoma therapy resistance.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
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- Perspective in the Mechanisms for Repairing Sperm DNA Damage.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair.Cancer biology & therapy · 2023Article
- ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex.Nucleic acids research · 2023Article
- Cancer chemoresistance and its mechanisms: Associated molecular factors and its regulatory role.Medical oncology (Northwood, London, England) · 2023Review
- Aflatoxin B1-DNA adducts modify the effects of post-operative adjuvant transarterial chemoembolization improving hepatocellular carcinoma prognosis.Exploration of targeted anti-tumor therapy · 2023Article
- Targeting the DNA Damage Response Machinery for Lung Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2022Review
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- The role of extracellular vesicles and interleukin-8 in regulating and mediating neutrophil-dependent cancer drug resistance.Frontiers in oncology · 2022Review
- Three-Dimensional Cell Culture Models of Hepatocellular Carcinoma - a Review.Journal of gastrointestinal cancer · 2021Review
- The component of the mJournal of experimental & clinical cancer research : CR · 2021Article
- Role of HMGB1 in Cisplatin-Persistent Lung Adenocarcinoma Cell Lines.Frontiers in oncology · 2021Article
- DNA Damage Repair Status Predicts Opposite Clinical Prognosis Immunotherapy and Non-Immunotherapy in Hepatocellular Carcinoma.Frontiers in immunology · 2021Article
- Inhibition of SETMAR-H3K36me2-NHEJ repair axis in residual disease cells prevents glioblastoma recurrence.Neuro-oncology · 2020Article
- Doxorubicin-Induced Translocation of mtDNA into the Nuclear Genome of Human Lymphocytes Detected Using a Molecular-Cytogenetic Approach.International journal of molecular sciences · 2020Article
- Review
- Inhibition of HMGB1 Overcomes Resistance to Radiation and Chemotherapy in Nasopharyngeal Carcinoma.OncoTargets and therapy · 2020Article
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- Heterogeneous nuclear ribonucleoprotein L facilitates recruitment of 53BP1 and BRCA1 at the DNA break sites induced by oxaliplatin in colorectal cancer.Cell death & disease · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA repair pathways are used by cancer cells to overcome many standard anticancer treatments, causing therapy resistance. Here, we investigated the role of XRCC4-like factor (XLF), a core member of the non-homologous end joining (NHEJ) repair pathway, in chemoresistance in hepatocellular carcinoma (HCC).
methodsqRT-PCR analysis and western blotting were performed to detect expression levels of genes and proteins related to NHEJ. NHEJ repair capacity was assessed in vitro (cell-free) and in vivo by monitoring the activity of the NHEJ pathway. Cell viability and IC50 assays were used to measure sensitivity to drug therapy. A xenograft HCC model was used to develop methods of targeting XLF-induced chemosensitization. Clinicopathological analysis was conducted on patients with HCC treated with transarterial chemoembolization (TACE).
resultsMany conventional cancer chemotherapeutics induce DNA double-strand breaks (DSBs). HCC cells respond to these breaks by increasing their NHEJ activity, resulting in resistance. XLF-knockdown cells show an inhibition of NHEJ activity in both cell-free and live-cell assays as well as a high level of unrepaired cellular DSBs. These results indicate that XLF facilitates DNA end-joining and therefore promotes NHEJ activity in cancer cells. Consequently, knockdown of XLF significantly chemosensitized resistant cells both in vitro and in xenograft tumors. A low rate of XLF genomic alteration was found in patients with primary HCC, but XLF expression was induced after drug treatment. Clinically, a high level of XLF expression is significantly associated with advanced HCC and shorter overall survival.
conclusionChemotherapy-induced overexpression of XLF and XLF-mediated enhancements in NHEJ activity contribute to chemoresistance in HCC cells and patients with HCC. Targeting XLF to modulate DSB repair could enhance drug sensitivity and may be a therapeutically useful addition to conventional therapy.
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