title: LF-MF inhibits iron metabolism and suppresses lung cancer through activation of P53-miR-34a-E2F1/E2F3 pathway.
abstract: Our previous studies showed that low frequency magnetic fields (LF-MF) suppressed tumor growth and influenced the function of immune system. Nevertheless the mechanisms behind the effect of LF-MF still remain to be elucidated. In this study, Tumor- bearing mice subcutaneously inoculated with Lewis lung cancer cells were exposed to a LF-MF (0.4T, 7.5 Hz) for 35 days and Survival rate, tumor growth and the tumor markers were measured. Results showed that tumor growth was obviously inhibited with a prolonged survival of tumor- bearing mice by LF-MF exposure. In vitro experiments, LF-MF was found to induce cell growth arrest, cell senescence and inhibit iron metabolism of lung cancer cells. Moreover, LF-MF stabilized p53 protein via inhibiting cell iron metabolism and the stabilized p53 protein enhanced miR-34a transcription. Furthermore, increased expression of miR-34a induced cell proliferation inhibition, cell cycle arrest and cell senescence of lung cancer cells by targeting E2F1/E2F3. We also detected the relevant indicator in tumor tissue such as the iron content, the level of miR-34a and related protein, corresponding results were obtained. Taken together, these observations imply that LF-MF suppressed lung cancer via inhibiting cell iron metabolism, stabilizing p53 protein and activation P53- miR-34a-E2F1/E2F3 pathway.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Qianyun
authors.initials: Q
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Shi
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Xiujun
authors.identifier: http://orcid.org/0000-0001-7027-3811
authors.initials: X
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Ji
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
authors.forename: Dongya
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, 210093, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. wangtt@nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China. wangtt@nju.edu.cn.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. yayihou@nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China. yayihou@nju.edu.cn.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004195:Disease Models, Animal; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D050699:E2F3 Transcription Factor / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D060526:Magnetic Fields; D053858:Metabolic Networks and Pathways / Q000528:radiation effects; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D055550:Protein Stability / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D007501:Iron