Adenovirus-mediated expression of UHRF1 reduces the radiosensitivity of cervical cancer HeLa cells to gamma-irradiation.
OBJECTIVE
An in vitro study was carried out to determine the effect of UHRF1 overexpression on radiosensitivity in human cervical cancer HeLa cells using adenovirus-mediated UHRF1 gene transfer (Ad5-UHRF1).


METHODS
Cell survival was evaluated using the clonogenic survival assay and the MTT assay; apoptosis and cell cycle distribution were monitored by flow cytometry. Protein levels were measured by Western blotting. Silencing XRCC4 expression was performed by transfection of small interfering RNA (siRNA).


RESULTS
Increased expression of UHRF1 by Ad5-UHRF1 significantly reduced the radiosensitivity of HeLa cells. The UHRF1-mediated radioresistance was correlated with increased DNA repair capability and increased expression of the DNA damage repair protein, XRCC4. Knocking down XRCC4 expression in the cells using XRCC4 siRNA markedly reduced the UHRF1-mediated radioresistance.


CONCLUSIONS
These results provide the first evidence for revealing a functional role of UHRF1 in human cervical cancer cells as a negative regulator of radiosensitivity.
Li
Xin-li
XL
School of Radiology and Public Health, Soochow University, Suzhou, China.
Meng
Qing-hui
QH
Fan
Sai-jun
SJ
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000528:radiation effects; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology; D005260:Female; D005720:Gamma Rays; D006367:HeLa Cells; D006801:Humans; D011836:Radiation Tolerance; D044767:Ubiquitin-Protein Ligases; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C101467:XRCC4 protein, human; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases