Abstract

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.

Keywords: Binding Sites, Apoptosis - radiation effects, Case-Control Studies, Cell Survival - radiation effects, Gene Knockdown Techniques, Hela Cells, Papillomaviridae, Papillomavirus Infections - radiotherapy, RNA, Neoplasm - metabolism, Radiation Tolerance - physiology, Tumor Suppressor Protein p53 - metabolism, Ubiquitin-Protein Ligases - metabolism, Uterine Cervical Neoplasms - radiotherapy