title: The role of TGF-β1-miR-21-ROS pathway in bystander responses induced by irradiated non-small-cell lung cancer cells.
abstract: BACKGROUND
  Many studies have indicated an important implication of radiation-induced bystander effects (RIBEs) in cancer radiotherapy, but the detailed signalling remains unclear.
  
  
  METHODS
  The roles of tumour growth factor-beta1 (TGF-β1) and miR-21 in medium-mediated RIBEs in H1299 non-small-cell lung cancer cells were investigated using DNA damage, changes in proliferation and levels of reactive oxygen species (ROS) as end points. SB431542, a specific inhibitor of TGF-β type 1 receptor kinases, was used to inhibit TGF-β1 pathways in irradiated and bystander cells. Exogenous miR-21 regulation was achieved through inhibitor or mimic transfection.
  
  
  RESULTS
  Compared with relative sham-radiation-conditioned medium, radiation-conditioned medium (RCM) from irradiated cells 1 h post radiation (1-h RCM) caused an increase in ROS levels and DNA damage in bystander cells, while 18-h RCM induced cell cycle delay and proliferation inhibition. All these effects were eliminated by TGF-βR1 inhibition. One-hour RCM upregulated miR-21 expression in bystander cells, and miR-21 inhibitor abolished bystander oxidative stress and DNA damage. Eighteen-hour RCM downregulated miR-21 of bystander cells, and miR-21 mimic eliminated bystander proliferation inhibition. Furthermore, the dysregulation of miR-21 was attenuated by TGF-βR1 inhibition.
  
  
  CONCLUSIONS
  The TGF-β1-miR-21-ROS pathway of bystander cells has an important mediating role in RIBEs in H1299 cells.
authors.affiliation: 1] School of Radiation Medicine and Protection, Medical College of Soochow University/School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China [2] Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 1] School of Radiation Medicine and Protection, Medical College of Soochow University/School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China [2] Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1] School of Radiation Medicine and Protection, Medical College of Soochow University/School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China [2] Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.
authors.forename: W
authors.initials: W
authors.lastname: Tian
authors.affiliation: 1] School of Radiation Medicine and Protection, Medical College of Soochow University/School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China [2] Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.
authors.forename: X
authors.initials: X
authors.lastname: Yin
authors.affiliation: 1] School of Radiation Medicine and Protection, Medical College of Soochow University/School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China [2] Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1] School of Radiation Medicine and Protection, Medical College of Soochow University/School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China [2] Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D024201:Bystander Effect / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004149:Dioxoles / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D047908:Intracellular Signaling Peptides and Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C498301:TP53BP1 protein, human; D053773:Transforming Growth Factor beta1; D000071857:Tumor Suppressor p53-Binding Protein 1