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电离辐射治疗后前列腺癌细胞的综合微小RNA谱分析。

Comprehensive microRNA profiling of prostate cancer cells after ionizing radiation treatment.

作者信息

Leung Chung-Man, Li Sung-Chou, Chen Ting-Wen, Ho Meng-Ru, Hu Ling-Yueh, Liu Wen-Shan, Wu Tony T, Hsu Ping-Chi, Chang Hong-Tai, Tsai Kuo-Wang

机构信息

Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.

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.

出版信息

Oncol Rep. 2014 Mar;31(3):1067-78. doi: 10.3892/or.2014.2988. Epub 2014 Jan 21.

Abstract

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.

摘要

微小RNA(miRNA)是一类小的非编码RNA,可负向调节基因表达,并已成为人类癌症辐射反应中的潜在生物标志物。在前列腺癌的辐射反应中仅鉴定出少数几种miRNA,并且辐射相关的miRNA机制在前列腺癌细胞对辐射的反应中的作用尚未完全了解。因此,本研究的目的是使用下一代测序(NGS)方法全面研究经辐射处理的PC3细胞中辐射反应性miRNA的表达水平、臂选择偏好和异构体。我们的数据显示,辐射暴露后前列腺癌中miRNA的臂选择偏好和3'修饰可能会发生改变。此外,PC3辐射处理后,读数末端AA二核苷酸修饰的比例随时间呈依赖性逐渐增加。我们还鉴定出6种miRNA在暴露于10 Gy辐射后表达增加,16种miRNA表达减少。通路富集分析显示,这些辐射诱导的miRNA的靶基因显著共同调节辐射反应通路,包括丝裂原活化蛋白激酶(MAPK)、Wnt、转化生长因子-β(TGF-β)和ErbB信号通路。此外,对癌症基因组图谱(TCGA)数据库的分析显示,这些辐射诱导的miRNA的表达在前列腺癌中经常失调。我们的研究鉴定出了可能有助于放射敏感性并可作为放射治疗生物标志物的辐射诱导的miRNA候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca7/3926670/aa1cb31e18cb/OR-31-03-1067-g00.jpg

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