title: DNA damage-induced NF-κB activation in human glioblastoma cells promotes miR-181b expression and cell proliferation.
abstract: BACKGROUND
  Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. After surgery, radiotherapy is the mainstay of treatment for GBM patients. Unfortunately, the vast majority of GBM patients fail responding to radiotherapy because GBM cells remain highly resistant to radiation. Radiotherapy-induced DNA damage response may correlate with therapeutic resistance.
  
  
  METHODS
  Ionizing radiation (IR) was used to induce DNA damage. Cell proliferation and migration were detected by wound-healing, MTT and apoptosis assays. Dual-luciferase assays and Western blot analysis were performed to evaluate NF-κB activation and validate microRNA targets. Real-time PCR was used to study mRNA and microRNA levels.
  
  
  RESULTS
  IR-induced DNA damage activated NF-κB in GBM cells which promoted expression of IL-6, IL-8 and Bcl-xL, thereby contributing to cell survival and invasion. Knockdown SENP2 expression enhanced NF-κB essential modulator (NEMO) SUMOylation and NF-κB activity following IR exposure. miR-181b targets SENP2 and positively regulated NF-κB activity.
  
  
  CONCLUSIONS
  NF-κB activation by DNA damage in GBM cells confers resistance to radiation-induced death.
authors: Department of Neurosurgery, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Rui-Xue
authors: RX
authors: Xu
authors: Rong-Yao
authors: RY
authors: Liu
authors: Chun-Ming
authors: CM
authors: Wu
authors: Yong-Shun
authors: YS
authors: Zhao
authors: Yang
authors: Y
authors: Li
authors: Yi-Qun
authors: YQ
authors: Yao
authors: Ying-Hui
authors: YH
authors: Xu
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human