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miR-375 Modulates Radiosensitivity of HR-HPV-Positive Cervical Cancer Cells by Targeting UBE3A through the p53 Pathway

Lili Song, Shikai Liu, Saitian Zeng, Liang Zhang, Xia Li

(Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland))

Med Sci Monit 2015; 21:2210-2217

DOI: 10.12659/MSM.893859

BACKGROUND: Prediction of radioresistance of HR-HPV-positive (+) cervical cancer, especially before the course of radiotherapy, is quite beneficial to develop an optimal treatment strategy for individual patients. Unfortunately, the mechanisms responsible for radioresistance of cervical cancer are still largely unexplored. HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression. In this study, we explored the association between miR-375 and radioresistance in HR-HPV (+) cervical cancer.
MATERIAL AND METHODS: qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa cervical cancer cell lines. The influence of miR-375 on radiosensitivity and the downstream regulative network were further explored in the cell line models.
RESULTS: The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression. UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis.
CONCLUSIONS: The miR-375-UBE3A axis is important in modulating radiosensitivity of HR-HPV (+) cervical cancer.

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