title: MicroRNA-449a enhances radiosensitivity by downregulation of c-Myc in prostate cancer cells.
abstract: MicroRNAs (miRNAs) have been reported to be involved in DNA damage response induced by ionizing radiation (IR). c-Myc is reduced when cells treated with IR or other DNA damaging agents. It is unknown whether miRNAs participate in c-Myc downregulation in response to IR. In the present study, we found that miR-449a enhanced radiosensitivity in vitro and in vivo by targeting c-Myc in prostate cancer (LNCaP) cells. MiR-449a was upregulated and c-Myc was downregulated in response to IR in LNCaP cells. Overexpression of miR-449a or knockdown of c-Myc promoted the sensitivity of LNCaP cells to IR. By establishing c-Myc as a direct target of miR-449a, we revealed that miR-449a enhanced radiosensitivity by repressing c-Myc expression in LNCaP cells. Furthermore, we showed that miR-449a enhanced radiation-induced G2/M phase arrest by directly downregulating c-Myc, which controlled the Cdc2/CyclinB1 cell cycle signal by modulating Cdc25A. These results highlight an unrecognized mechanism of miR-449a-mediated c-Myc regulation in response to IR and may provide alternative therapeutic strategies for the treatment of prostate cancer.
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000, PR China.|Institute of Gansu Medical Science Research, Lanzhou 730050, PR China.|University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Mao
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|University of Chinese Academy of Sciences, Beijing 100039, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, PR China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Si
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000, PR China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D004847:Epithelial Cells / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011836:Radiation Tolerance
chemical_list: C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc