title: miR-375 Modulates Radiosensitivity of HR-HPV-Positive Cervical Cancer Cells by Targeting UBE3A through the p53 Pathway.
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.
  
  
  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.
authors.affiliation: Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland).
authors.forename: Lili
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland).
authors.forename: Shikai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland).
authors.forename: Saitian
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland).
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland).
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001665:Binding Sites; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D005260:Female; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism* / Q000532:radiotherapy; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics* / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000532:radiotherapy
chemical_list: C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases