@Article{096504018X15154085345907,
AUTHOR = {Fei Li, Bin Liu, Xiaolan Zhou, Quan Xu},
TITLE = {Silencing of E3 Ubiquitin Ligase RNF8 Enhances Ionizing Radiation Sensitivity  of Medulloblastoma Cells by Promoting the Deubiquitination of PCNA},
JOURNAL = {Oncology Research},
VOLUME = {26},
YEAR = {2018},
NUMBER = {9},
PAGES = {1365--1373},
URL = {http://www.techscience.com/or/v26n9/56766},
ISSN = {1555-3906},
ABSTRACT = {DNA damage response induced by ionizing radiation (IR) is an important event involved in the sensitivity and 
efficiency of radiotherapy in human medulloblastoma. RNF8 is an E3 ubiquitin ligase and has key roles in 
the process of DNA damage and repair. Our study aimed to evaluate the effect of RNF8 in the DNA damage 
repair induced by IR exposure in medulloblastoma cells. We found that the levels of RNF8 were significantly 
upregulated by γ-ray irradiation in a dose-dependent manner in medulloblastoma cells and colocalized with 
γ-H2AX, a sensitive marker of DNA double-strand breaks induced by γ-ray radiation. RNF8 knockdown was 
observed to enhance the sensitivity of IR in medulloblastoma cells, as evaluated by reduced cell survival. The 
apoptosis and cell cycle arrest of medulloblastoma cells were dramatically increased by RNF8 suppression 
after IR treatment. Furthermore, RNF8 inhibition did not affect the protein levels of BRCA1, a crucial protein involved in IR-induced DNA damage repair, but significantly decreased the recruitment of BRCA1 and 
increased the level of γ-H2AX at DNA damage sites compared to the control. A significant increase in OTM 
was observed in medulloblastoma cells treated by RNF8 shRNA after exposure to IR, indicating the effect of 
RNF8 on DNA damage and repair. Additionally, PCNA, a major target for ubiquitin modification during DNA 
damage response, was found to be monoubiquitinated by E3 ligase RNF8 and might contribute to the low 
radiosensitivity in medulloblastoma cells. Altogether, our findings may provide RNF8 as a novel target for the 
improvement of radiotherapy in medulloblastoma.},
DOI = {10.3727/096504018X15154085345907}
}