McDermott Niamh, Meunier Armelle, Wong Simon, Buchete Vio, Marignol Laure
Trinity Translational Medicine Institute, Translational Radiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Discipline of Radiation Therapy, Trinity College Dublin, Ireland.
Irish Centre for High-End Computing, National University of Ireland, Galway, Ireland.
Clin Transl Radiat Oncol. 2017 Feb 17;2:63-68. doi: 10.1016/j.ctro.2017.01.005. eCollection 2017 Feb.
miRNAs are increasingly associated with the aggressive phenotype of prostate tumours. Their ability to control radiobiologically-relevant cellular processes strengthens their potential as novel markers of response to radiation therapy.
To identify miRNAs associated with increased clonogenic survival following radiation exposure.
The miRNA expression profiles of a panel of 22RV1 cells with varying levels of radiosensitivities (hypoxic H-22Rv1 cells, RR-22Rv1 cells derived from WT-22Rv1 cells through 2-Gy fractionated repeated exposure, the associated aged matched cells (AMC-22Rv1) and the WT-22Rv1 cell lines) were generated and cross-analysed to identify common miRNAs associated with a radioresistant phenotype.
Increased clonogenic survival following irradiation was associated with significant modifications in miRNA expression pattern. miR-221 (up) and miR-4284 (down) in RR-22Rv1 and MiR-31 and miR-200c in AMC-22Rv1 were the most uniquely significantly deregulated miRNAs when compared to WT-22Rv1 cells. miR-200c ranked as the most downregulated miRNAs in hypoxic, when compared to RR-22Rv1 cells. miR-200a was the only differentially expressed miRNA between RR-22Rv1 and AMC-22Rv1 cells. miR-210 yielded the highest fold change in expression in H-22Rv1, when compared to WT-22RV1 cells.
This study identifies candidate miRNAs for the development of novel prognostic biomarkers for radiotherapy prostate cancer patients.
微小RNA（miRNA）与前列腺肿瘤的侵袭性表型越来越相关。它们控制放射生物学相关细胞过程的能力增强了其作为放射治疗反应新标志物的潜力。
鉴定与辐射暴露后克隆形成存活率增加相关的miRNA。
生成并交叉分析了一组具有不同放射敏感性水平的22RV1细胞（缺氧的H-22Rv1细胞、通过2 Gy分次重复照射从WT-22Rv1细胞衍生而来的RR-22Rv1细胞、相关的年龄匹配细胞（AMC-22Rv1）和WT-22Rv1细胞系）的miRNA表达谱，以鉴定与放射抗性表型相关的常见miRNA。
照射后克隆形成存活率增加与miRNA表达模式的显著改变有关。与WT-22Rv1细胞相比，RR-22Rv1中的miR-221（上调）和miR-4284（下调）以及AMC-22Rv1中的MiR-31和miR-200c是最独特且显著失调的miRNA。与RR-22Rv1细胞相比，miR-200c在缺氧条件下是下调最明显的miRNA。miR-200a是RR-22Rv1和AMC-22Rv1细胞之间唯一差异表达的miRNA。与WT-22RV1细胞相比，miR-210在H-22Rv1中的表达变化倍数最高。
本研究确定了用于开发前列腺癌放疗患者新型预后生物标志物的候选miRNA。
