RAD18 mediates resistance to ionizing radiation in human glioma cells
| Autor: | Chen Xie, Hong-Bin Cheng, Hongwei Wang, Wu Yue, Zhi Wang, Jianhua Li |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male DNA Repair Cell Survival DNA damage Ubiquitin-Protein Ligases Blotting Western Biophysics Apoptosis Biology Radiation Tolerance Biochemistry Histones Cell Line Tumor Radiation Ionizing Radioresistance Glioma medicine Humans Radiosensitivity Molecular Biology Cells Cultured Aged Gene knockdown Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Dose-Response Relationship Radiation Cell Biology Middle Aged medicine.disease nervous system diseases DNA-Binding Proteins Gene Expression Regulation Neoplastic Microscopy Fluorescence Cell culture Cancer research Female RNA Interference Ectopic expression Neoplasm Recurrence Local Glioblastoma |
| Zdroj: | Biochemical and Biophysical Research Communications. 445:263-268 |
| ISSN: | 0006-291X |
| Popis: | Radioresistance remains a major challenge in the treatment of glioblastoma multiforme (GBM). RAD18 a central regulator of translesion DNA synthesis (TLS), has been shown to play an important role in regulating genomic stability and DNA damage response. In the present study, we investigate the relationship between RAD18 and resistance to ionizing radiation (IR) and examined the expression levels of RAD18 in primary and recurrent GBM specimens. Our results showed that RAD18 is an important mediator of the IR-induced resistance in GBM. The expression level of RAD18 in glioma cells correlates with their resistance to IR. Ectopic expression of RAD18 in RAD18-low A172 glioma cells confers significant resistance to IR treatment. Conversely, depletion of endogenous RAD18 in RAD18-high glioma cells sensitized these cells to IR treatment. Moreover, RAD18 overexpression confers resistance to IR-mediated apoptosis in RAD18-low A172 glioma cells, whereas cells deficient in RAD18 exhibit increased apoptosis induced by IR. Furthermore, knockdown of RAD18 in RAD18-high glioma cells disrupts HR-mediated repair, resulting in increased accumulation of DSB. In addition, clinical data indicated that RAD18 was significantly higher in recurrent GBM samples that were exposed to IR compared with the corresponding primary GBM samples. Collectively, our findings reveal that RAD18 may serve as a key mediator of the IR response and may function as a potential target for circumventing IR resistance in human GBM. |
| Databáze: | OpenAIRE |
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