title: miR-511 induces the apoptosis of radioresistant lung adenocarcinoma cells by triggering BAX.
abstract: Radioresistance is one of the main reasons for the failure of radiotherapy in lung cancer. The present study was conducted to identify the role of miR-511 in suppressing the growth of radioresistant lung adenocarcinoma cells. First, a radioresistant A549/R cell line was generated after prolonged exposure to X-rays for 68 Gy (2 Gy/day, 5 days/week) and the radioresistance was confirmed by wound healing assay. Next, oncogenic TRIB2 was found to be upregulated in the radioresistant A549/R cells when compared to that of the control A549 cells as determined by western blot analysis. As the upstream miRNA, quantitative PCR showed that miR-511 expression was decreased in the radioresistant A549/R cells. Overexpression of miR-511 in miR-511-transfected A549/R cells inhibited cell growth and increased the number of apoptotic cells when compared with the control treatment. Flow cytometric analysis further demonstrated that the growth suppressive effect of miR-511 on A549/R cells was mediated by regulation of the cell cycle, most likely due to a block in the G1-S transition. Finally, our results showed that the expression of BAX was lower in the radioresistant A549/R cells when compared with that in the control A549 cells. After downregulation of TRIB2 by miR-511 treatment, BAX expression was obviously increased in the miR-511-transfected apoptotic A549/R cells when compared to that in the NC-treated or control cultures. In summary, our results revealed that miR-511 regulates the growth of radioresistant A549/R cells by increasing BAX expression through TRIB2, which suggests that miR-511 may be a potential therapeutic molecule for the treatment of radioresistant lung adenocarcinoma.
authors.affiliation: Key Laboratory of Tumour Molecular Biology, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Han-Han
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Tumour Molecular Biology, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Pang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin 300060, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Key Laboratory of Tumour Molecular Biology, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Jia-Xuan
authors.initials: JX
authors.lastname: Xin
authors.affiliation: Key Laboratory of Tumour Molecular Biology, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: You-Jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin 300060, P.R. China.
authors.forename: Zi-Cheng
authors.initials: ZC
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264000, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Key Laboratory of Tumour Molecular Biology, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Ping-Yu
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan 250117, P.R. China.
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Li
authors.affiliation: Key Laboratory of Tumour Molecular Biology, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
authors.forename: Shu-Yang
authors.initials: SY
authors.lastname: Xie
mesh_terms: D000230:Adenocarcinoma; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms; D035683:MicroRNAs / Q000502:physiology*; D034622:RNA Interference; D011836:Radiation Tolerance; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D047908:Intracellular Signaling Peptides and Proteins; C578471:MIRN511 microRNA, human; D035683:MicroRNAs; D051028:bcl-2-Associated X Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human