title: Oleuropein enhances radiation sensitivity of nasopharyngeal carcinoma by downregulating PDRG1 through HIF1α-repressed microRNA-519d.
abstract: Oleuropein (OL) is a well-known anti-oxidative agent and is shown to reduce the hypoxia-inducible factor 1 α (HIF1α) protein expression after radiation. The current study investigated the effects of OL on radiation response in nasopharyngeal carcinoma (NPC).
  
  
  
  Colony formation assay was performed to compare the radiation response in vitro. Xenograft mouse model was used to study the OL effects on radiation in vivo. Chromatin immunoprecipitation and luciferase reporter assays were performed to identify the relations among HIF1α, miR-519d and PDRG1. Stable HIF1α or PDRG1 overexpression, and miR-519d downregulation were performed to test the radiation response both in vitro and in vivo.
  
  
  
  OL strongly enhanced radiosensitivity of NPC cells both in vitro and in vivo. Chromatin immunoprecipitation and luciferase reporter assays suggested miR-519d was a direct target of HIF1α, and PDRG1 was a direct target of miR-519d. Overexpression of HIF1α or PDRG1, and downregulation of miR-519d abolished the radiation sensitizing effects of OL.
  
  
  
  Our study hereby demonstrates OL is a radiation sensitizing agent in NPC both in vivo and in vitro. OL treatment reduces the activity of HIF1α-miR-519d-PDRG1 pathway, which is essential to the radiosensitizing effects of OL.
authors.affiliation: Department of Otorhinolarynogology, The Second People's Hospital of Wuxi, Nanjing Medical University, 68 Zhongshan Road, Wuxi, 214002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Otorhinolarynogology, The Second People's Hospital of Wuxi, Nanjing Medical University, 68 Zhongshan Road, Wuxi, 214002, China. xiaodj2125@126.com.
authors.forename: Dajiang
authors.initials: D
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D057888:Iridoid Glucosides; D039823:Iridoids / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D057888:Iridoid Glucosides; D039823:Iridoids; C546194:MIRN519 microRNA, human; D035683:MicroRNAs; C478985:PDRG1 protein, human; D011838:Radiation-Sensitizing Agents; C002769:oleuropein
keywords: HIF1α; Nasopharyngeal carcinoma; Oleuropein; Radiation sensitivity; miR-519d