ArticleOncotarget2015
DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Fragile histidine triad (FHIT) suppresses gastric cancer via translational regulation of the epigenetic modifier KDM6B.The Journal of biological chemistry · 2026Article
- Diterpenoid fromInternational journal of molecular sciences · 2024Article
- Article
- Radioresistance and brain metastases: a review of the literature and applied perspective.Frontiers in oncology · 2024Review
- Article
- Epigenetic methylation changes: implication as biomarkers in oral and maxillofacial area cancers.Medicine and pharmacy reports · 2023Article
- Z-Ligustilide Induces c-Myc-Dependent ApoptosisFrontiers in oncology · 2022Article
- Endoplasmic Reticulum Stress of Oral Squamous Cell Carcinoma Induces Immunosuppression of Neutrophils.Frontiers in oncology · 2022Article
- Article
- Biological Adaptations of Tumor Cells to Radiation Therapy.Frontiers in oncology · 2021Review
- IRAK2, an IL1R/TLR Immune Mediator, Enhances RadiosensitivityFrontiers in oncology · 2021Article
- Effects of FHIT gene on proliferation and apoptosis of osteosarcoma cells.Oncology letters · 2019Article
- The pivotal role of DNA methylation in the radio-sensitivity of tumor radiotherapy.Cancer medicine · 2018Review
- Impact of DNA and RNA Methylation on Radiobiology and Cancer Progression.International journal of molecular sciences · 2018Review
- Article
- Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinomaOncotarget · 2017Article
- Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response.PLoS genetics · 2016Review
- SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma.BMC cancer · 2015Article
- XRCC2 as a predictive biomarker for radioresistance in locally advanced rectal cancer patients undergoing preoperative radiotherapy.Oncotarget · 2015Article
- Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using a methylation microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation, H3K27me3 and overexpression of methyltransferase EZH2 in OML1-R cells. Epigenetic interventions or depletion of EZH2 restored FHIT expression. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models, while also resensitizing radioresistant cancer cells to irradiation, by restoring Chk2 phosphorylation and G2/M arrest. Clinically, promoter hypermethylation of FHIT inversely correlated with its expression and independently predicted both locoregional control and overall survival in 40 match-paired oral cancer patient samples. Further in vivo therapeutic experiments confirmed that inhibition of DNA methylation significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation.
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