title: miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM.
abstract: Increasing number of studies report that microRNAs play important roles in radiosensitization. miR-30a has been proved to perform many functions in the development and treatment of cancer, and it is downregulated in non-small cell lung cancer (NSCLC) tissues and cells. This study was conducted to understand if miR-30a plays a role in the radiosensitivity of NSCLC cells. Radiosensitivity was examed by colony survival assay and tumor volume changing in vitro and in vivo, respectively. Bioinformatic analysis and luciferase reporter assays were used to distinguish the candidate target of miR-30a. qRT-PCR and western blotting were carried out to detect the relative expression of mRNAs and proteins. Cell cycle and cell apoptosis were determined by flow cytometry. Our results illustrated miR-30a could increase the radiosensitivity of NSCLC, especially in A549 cell line. In vivo experiment also showed the potential radiosensitizing possibility of miR-30a. Further exploration validated that miR-30a was directly targ-eting activating transcription factor 1 (ATF1). In studying the ataxia-telangiectasia mutated (ATM) associated effects on cell radiosensitivity, we found that miR-30a could reduce radiation induced G2/M cell cycle arrest and may also affect radiation induced apoptosis. Together, our results demonstrated that miR-30a may modulate the radiosensitivity of NSCLC through reducing the function of ATF1 in phosphorylation of ATM and have potential therapeutic value.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wenze
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tuotuo
authors.initials: T
authors.lastname: Gong
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Beina
authors.initials: B
authors.lastname: Hui
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000072283:A549 Cells; D051697:Activating Transcription Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000096:biosynthesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C531110:ATF1 protein, human; D051697:Activating Transcription Factor 1; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins