title: miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells.
abstract: miR-449a, a novel tumor suppressor, is deregulated in various malignancies, including prostate cancer. Overexpression of miR-449a induces cell cycle arrest, apoptosis, and senescence, but its role in response to ionizing radiation and underlying molecular mechanism are still unknown. Here, we report that miR-449a enhances radiation-induced G2/M phase arrest and apoptosis through modulating pRb/E2F1 and sensitizes prostate cancer cells to X-ray radiation. In wild-type Rb PC-3 cells, overexpression of miR-449a enhances radiation-induced G2/M arrest and apoptosis and promotes the sensitivity to X-ray radiation. While mutant Rb DU-145 cells are resistant to the X-ray radiation despite in the presence of miR-449a. The cell cycle distribution of DU-145 cells is not significantly altered by miR-449a in the response to ionizing radiation. Furthermore, elevated miR-449a downregulates cell cycle regulator CDC25A and oncogene HDAC1. By targeting genes involved in controlling pRb/E2F1 activity, miR-449a regulates cell cycle progression and apoptosis and consequently enhances the radiosensitivity of PC-3 cells. Thus, miR-449a, as a miRNA component of the Rb pathway, promotes the radiosensitivity of PC-3 cells through regulating pRb/E2F1.
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|School of Nuclear Science and Technology, Lanzhou University, Lanzhou, 730000, People's Republic of China.|Institute of Gansu Medical Science Research, Lanzhou, 730050, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, 100039, People's Republic of China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Mao
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, 100039, People's Republic of China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Di
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Si
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China. zhangh@impcas.ac.cn.|Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, People's Republic of China. zhangh@impcas.ac.cn.|Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, People's Republic of China. zhangh@impcas.ac.cn.|Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, 730000, China. zhangh@impcas.ac.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D050687:E2F1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D011467:Prostate / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000528:radiation effects; D014965:X-Rays
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D016160:Retinoblastoma Protein
keywords: Apoptosis; G2/M arrest; Prostate cancer; Radiosensitivity; miR-449a; pRb/E2F1