Palayoor Sanjeewani T, John-Aryankalayil Molykutty, Makinde Adeola Y, Falduto Michael T, Magnuson Scott R, Coleman C Norman
Authors' Affiliations: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and
Authors' Affiliations: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and.
Mol Cancer Res. 2014 Jul;12(7):1002-15. doi: 10.1158/1541-7786.MCR-13-0623. Epub 2014 Apr 30.
Although modern radiotherapy technologies can precisely deliver higher doses of radiation to tumors, thus, reducing overall radiation exposure to normal tissues, moderate dose, and normal tissue toxicity still remains a significant limitation. The present study profiled the global effects on transcript and miR expression in human coronary artery endothelial cells using single-dose irradiation (SD, 10 Gy) or multifractionated irradiation (MF, 2 Gy × 5) regimens. Longitudinal time points were collected after an SD or final dose of MF irradiation for analysis using Agilent Human Gene Expression and miRNA microarray platforms. Compared with SD, the exposure to MF resulted in robust transcript and miR expression changes in terms of the number and magnitude. For data analysis, statistically significant mRNAs (2-fold) and miRs (1.5-fold) were processed by Ingenuity Pathway Analysis to uncover miRs associated with target transcripts from several cellular pathways after irradiation. Interestingly, MF radiation induced a cohort of mRNAs and miRs that coordinate the induction of immune response pathway under tight regulation. In addition, mRNAs and miRs associated with DNA replication, recombination and repair, apoptosis, cardiovascular events, and angiogenesis were revealed.
Radiation-induced alterations in stress and immune response genes in endothelial cells contribute to changes in normal tissue and tumor microenvironment, and affect the outcome of radiotherapy.
尽管现代放疗技术能够精确地向肿瘤输送更高剂量的辐射，从而减少对正常组织的总体辐射暴露，但中等剂量以及正常组织毒性仍然是一个重大限制。本研究使用单剂量照射（SD，10 Gy）或分次照射（MF，2 Gy×5）方案，分析了对人冠状动脉内皮细胞转录本和miR表达的整体影响。在SD照射后或MF照射的最后一剂后收集纵向时间点，使用安捷伦人类基因表达和miRNA微阵列平台进行分析。与SD相比，MF照射导致转录本和miR表达在数量和幅度方面发生显著变化。对于数据分析，通过Ingenuity通路分析处理具有统计学意义的mRNA（2倍）和miR（1.5倍），以揭示照射后来自几个细胞通路的与靶转录本相关的miR。有趣的是，MF辐射诱导了一组在严格调控下协调免疫反应通路诱导的mRNA和miR。此外，还揭示了与DNA复制、重组和修复、细胞凋亡、心血管事件和血管生成相关的mRNA和miR。
辐射诱导的内皮细胞应激和免疫反应基因改变有助于正常组织和肿瘤微环境的变化，并影响放疗结果。
