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Comprehensive microRNA profiling of prostate cancer cells after ionizing radiation treatment

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MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression and have emerged as potential biomarkers in radiation response to human cancer. Only a few miRNAs have been identified in radiation response to prostate cancer and the involvement of the radiation-associated miRNA machinery in the response of prostate cancer cells to radiation is not thoroughly understood. Therefore, the purpose of the present study was to comprehensively investigate the expression levels, arm selection preference and isomiRs of radiation-response miRNAs in radiation-treated PC3 cells using a next-generation sequencing (NGS) approach. Our data revealed that the arm selection preference and 3' modification of miRNAs may be altered in prostate cancer after radiation exposure. In addition, the proportion of AA dinucleotide modifications at the end of the read gradually increased in a time-dependent manner after PC3 radiation treatment. We also identified 6 miRNAs whose expression increased and 16 miRNAs whose expression decreased after exposure to 10 Gy of radiation. A pathway enrichment analysis revealed that the target genes of these radiation-induced miRNAs significantly co-modulated the radiation response pathway, including the mitogen-activated protein kinase (MAPK), Wnt, transforming growth factor-β (TGF-β) and ErbB signaling pathways. Furthermore, analysis of The Cancer Genome Atlas (TCGA) database revealed that the expression of these radiation-induced miRNAs was frequently dysregulated in prostate cancer. Our study identified radiation-induced miRNA candidates which may contribute to radiosensitivity and can be used as biomarkers for radiotherapy.
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Document Type: Research Article

Affiliations: 1: Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. 2: Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C. 3: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, R.O.C. 4: Genomics Research Center, Academia Sinica, Taipei, Taiwan, R.O.C. 5: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, R.O.C. 6: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. 7: Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung, Taiwan, R.O.C. 8: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.

Publication date: March 1, 2014

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