title: MicroRNA-203 Modulates the Radiation Sensitivity of Human Malignant Glioma Cells.
abstract: OBJECTIVE
  We investigated whether miR-203 could modulate the radiation sensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved.
  
  
  METHODS
  Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR-203. Real-time PCR (RT-PCR), clonogenic assays, immunofluorescence, and invasion/migration assays were performed. To predict the target(s), bioinformatics analyses using microRNA target databases were performed.
  
  
  RESULTS
  Overexpression of miR-203 increased the radiation sensitivity of all 3 human MG cell lines and prolonged radiation-induced γ-H2AX foci formation. Bioinformatics analyses suggested that miR-203 could be involved in post-transcriptional control of DNA repair, PI3K/AKT, SRC, and JAK/STAT3 and the vascular signaling pathway. Western blot analysis validated the fact that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1α, and MMP2. Overexpression of miR-203 inhibited invasion and migration potentials, downregulated SLUG and Vimentin, and upregulated Claudin-1 and ZO1.
  
  
  CONCLUSIONS
  These data demonstrate that miR-203 potentially controls DNA damage repair via the PI3K/AKT and JAK/STAT3 pathways and may collectively contribute to the modulation of radiation sensitivity in MG cells by inhibiting DNA damage repair, prosurvival signaling, and epithelium-mesenchyme transition. Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radiation resistance of GBM.
authors.affiliation: Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido, Republic of Korea.
authors.forename: Yeo Hyun
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido, Republic of Korea.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido, Republic of Korea.
authors.forename: Dan Hyo
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido, Republic of Korea.
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hong-Gyun
authors.initials: HG
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul, Republic of Korea; Medical Science Research Institute, Seoul National University Bundang Hospital, Kyeonggido, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: inah228@snu.ac.kr.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Kim
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D062445:Claudin-1 / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics; D015536:Down-Regulation; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062445:Claudin-1; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C121623:PSMF1 protein, human; D011506:Proteins; C000604407:SNAI1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071250:Snail Family Transcription Factors; C569042:TJP1 protein, human; D014157:Transcription Factors; D014746:Vimentin; D062826:Zonula Occludens-1 Protein; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex