title: Modulation of NF-κB/miR-21/PTEN pathway sensitizes non-small cell lung cancer to cisplatin.
abstract: BACKGROUND
  Platinum-based chemotherapy is a standard strategy for non-small cell lung cancer (NSCLC), while chemoresistance remains a major therapeutic challenge in current clinical practice. Our present study was aimed to determine whether inhibition of the NF-κB/miR-21/PTEN pathway could increase the sensitivity of NSCLC to cisplatin.
  
  
  METHODS
  The expression of miR-21 in NSCLC tissues was determined using in situ hybridization. Next, the effect of miR-21 on the sensitivity of A549 cells to cisplatin was determined in vitro. Whether miR-21 regulated PTEN expression was assessed by luciferase assay. Furthermore, whether NF-κB targeted its binding elements in the miR-21 gene promoter was determined by luciferase and ChIP assay. Finally, we measured the cell viability and apoptosis under cisplatin treatment when NF-κB was inhibited.
  
  
  RESULTS
  An elevated level of miR-21 was observed in NSCLC lung tissues and was related to a short survival time. Exogenous miR-21 promoted cell survival when exposed to cisplatin, while miR-21 inhibition could reverse this process. The RNA and protein levels of PTEN were significantly decreased by exogenous miR-21, and the 3'-untranslated region of PTEN was shown to be a target of miR-21. The expression of miR-21 was regulated by NF-κB binding to its element in the promoter, a finding that was verified by luciferase and ChIP assay. Hence, inhibition of NF-κB by RNA silencing protects cells against cisplatin via decreasing miR-21 expression.
  
  
  CONCLUSIONS
  Modulation of the NF-κB/miR-21/PTEN pathway in NSCLC showed that inhibition of this pathway may increase cisplatin sensitivity.
authors: Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Zhenhua
authors: Z
authors: Yang
authors: Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Surong
authors: S
authors: Fang
authors: Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Yicheng
authors: Y
authors: Di
authors: Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Weiwei
authors: W
authors: Ying
authors: Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Yan
authors: Y
authors: Tan
authors: Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Wei
authors: W
authors: Gu
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D051059:PTEN Phosphohydrolase; D002945:Cisplatin