title: Downregulation of AATK mediates microRNA-558-induced resistance of A549 cells to radiotherapy.
abstract: The deregulation of microRNAs (miRNAs) is often implicated in the control of sensitivity to radiotherapy. The objective of the present study was to identify the association between miR‑558 and apoptosis‑associated tyrosine kinase (AATK), and their importance in regulating the development of resistance to radiotherapy. The current study demonstrated that AATK, a radiosensitization-associated gene, is a target of miR‑558 in lung cancer cells, using in silico analysis and a luciferase reporter system. Furthermore, it was determined that transfection of 30 or 50 nM miR‑558 mimics and AATK specific siRNA markedly suppressed the mRNA and protein expression of AATK. To determine whether miR‑558 was required for lung cancer cell radioresistance, A549 cells were treated with different doses of ionizing radiation, from 0 to 10 Gy, following transfection with miR‑558 mimics or AATK specific siRNA. It was determined that the administration of miR‑558 mimics or AATK specific siRNA alone did not significantly alter the survival rate of the cells. By contrast, in the cells exposed to 4, 6 or 8 Gy, the administration of miR‑558 mimics or AATK specific siRNA significantly promoted cell survival rate and overexpression of AATK reversed this effect. In conclusion, these data demonstrate that the miR‑558/AATK cascade is important for the radiosensitization of lung cancer cells and may be a potential radiotherapy target.
authors.affiliation: Department of Oncology, Central Hospital of Zaozhuang Mineral Group, Zaozhuang, Shandong 277800, P.R. China.
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Central Hospital of Zaozhuang Mineral Group, Zaozhuang, Shandong 277800, P.R. China.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Song
authors.affiliation: Department of Oncology, Central Hospital of Zaozhuang Mineral Group, Zaozhuang, Shandong 277800, P.R. China.
authors.forename: Jin-Shan
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Oncology, Central Hospital of Zaozhuang Mineral Group, Zaozhuang, Shandong 277800, P.R. China.
authors.forename: Qing-Ting
authors.initials: QT
authors.lastname: Yi
authors.affiliation: Department of Oncology, Central Hospital of Zaozhuang Mineral Group, Zaozhuang, Shandong 277800, P.R. China.
authors.forename: Bao-Jian
authors.initials: BJ
authors.lastname: Li
authors.affiliation: Department of Oncology, Central Hospital of Zaozhuang Mineral Group, Zaozhuang, Shandong 277800, P.R. China.
authors.forename: Si-Hai
authors.initials: SH
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000072283:A549 Cells; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001665:Binding Sites; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D011878:Radiotherapy
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C000603689:MIRN-558 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C118137:AATK protein, human; D011505:Protein-Tyrosine Kinases