title: MicroRNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are noncoding RNAs inhibiting expression of numerous target genes by posttranscriptional regulation. miRNA-221 and miRNA-222 (miRNA-221/-222) expression is elevated in radioresistant tumor cell lines; however, it is not known whether and how miRNAs control cellular responses to ionizing irradiation.
  
  
  METHODS
  We used bioinformatic analyses, luciferase reporter assay, and genetic knockdown and biochemical assays to characterize the regulation pathways of miRNA-221/-222 in response to radiation treatment.
  
  
  RESULTS
  We identified the PTEN gene as a target of miRNA-221/-222. Furthermore, we found that knocking down miRNA-221/-222 by antisense oligonucleotides upregulated PTEN expression. Upregulated PTEN expression suppressed AKT activity and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in tumor cells.
  
  
  CONCLUSIONS
  miRNA-221/-222 control radiation sensitivity by regulating the PTEN/AKT pathway and can be explored as novel targets for radiosensitization.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Chunzhi
authors.initials: C
authors.lastname: Zhang
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Cao
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Lv
authors.forename: Shizhu
authors.initials: S
authors.lastname: Yu
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Wang
authors.forename: Anling
authors.initials: A
authors.lastname: Zhang
authors.forename: Zhifan
authors.initials: Z
authors.lastname: Jia
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Chunying
authors.initials: C
authors.lastname: Yang
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishiyama
authors.forename: Bin S
authors.initials: BS
authors.lastname: Teh
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
mesh_terms: D017209:Apoptosis; D001483:Base Sequence / Q000235:genetics; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D014410:Tumor Stem Cell Assay
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; C525709:MIR221, human; C525710:MIR222, human; C494929:PTEN protein, human