Radiation-Induced Long Noncoding RNAs in a Mouse Model after Whole-Body Irradiation.
Radiation-Induced Long Noncoding RNAs in a Mouse Model after Whole-Body Irradiation.
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DOI：
10.1667/rr14891.1
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发表时间：
2018-03
影响因子：
3.4
通讯作者：
Coleman CN
中科院分区：
文献类型：
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作者：
Aryankalayil MJ;Chopra S;Levin J;Eke I;Makinde A;Das S;Shankavaram U;Vanpouille-Box C;Demaria S;Coleman CN
Aryankalayil，M.J.，Chopra，S.，Levin，J.，Eke，I.，Makinde，A.，Das，S.，Shankavaram，U.，Vanpouille-Box，C.，Demaria，S.和Coleman，C.N.全身照射后小鼠模型中辐射诱导的长非编码RNA。辐射。资源。 189, 251–263 (2018)。长非编码 RNA (lncRNA) 正在成为调节许多生物过程的关键分子，并与发育和疾病发病机制有关。癌症和正常组织对治疗反应的生物标志物在精准医学以及公共卫生和医疗管理中引起了极大的兴趣，例如用于评估意外或故意暴露后的辐射损伤。全血和其他体液中的循环和功能性 RNA，包括 microRNA (miRNA) 和 lncRNA，是作为生物标志物的潜在有价值的候选者。早期预测辐射暴露可能产生的急性、中间和延迟影响可以及时进行治疗干预。为了确定长非编码 RNA (lncRNA) 是否可以作为辐射生物剂量测定的生物标志物，我们在全身照射后的小鼠模型中进行了全基因组转录组分析。在照射后 16、24 和 48 小时，对从暴露于 1、2、4、8 和 12 Gy X 射线的小鼠全血中分离的总 RNA 进行了差异 lncRNA 表达模式的评估。假辐射动物作为对照。在不同时间点接受不同辐射剂量后，观察到lncRNA表达模式的显着变化。我们鉴定了几种辐射诱导的 lncRNA，这些 lncRNA 因 DNA 损伤反应和免疫反应而闻名。肿瘤蛋白 53 (P53)、Trp53cor1、Dino、Pvt1 和 Tug1 的长非编码 RNA 靶标以及 p53 的上游调节因子 Meg3 在辐射反应中发生改变。 Gm14005 (Morrbid) 和 Tmevpg1 在所有时间点和剂量上均受辐射调节。这两种 lncRNA 具有作为血液放射生物标志物的重要潜力； Gm14005 (Morrbid) 最近被证明在炎症反应中发挥着关键作用，而 Tmevpg1 则与干扰素 γ 的调节有关。精确的分子生物标志物可能涉及多种诱导分子，不仅能够开发和有效使用医疗对策，而且还可以用于检测和规避或减轻癌症放射治疗中的正常组织损伤。
Aryankalayil, M. J., Chopra, S., Levin, J., Eke, I., Makinde, A., Das, S., Shankavaram, U., Vanpouille-Box, C., Demaria, S. and Coleman, C. N. Radiation-Induced Long Noncoding RNAs in a Mouse Model after Whole-Body Irradiation. Radiat. Res. 189, 251–263 (2018). Long noncoding RNAs (lncRNAs) are emerging as key molecules in regulating many biological processes and have been implicated in development and disease pathogenesis. Biomarkers of cancer and normal tissue response to treatment are of great interest in precision medicine, as well as in public health and medical management, such as for assessment of radiation injury after an accidental or intentional exposure. Circulating and functional RNAs, including microRNAs (miRNAs) and lncRNAs, in whole blood and other body fluids are potential valuable candidates as biomarkers. Early prediction of possible acute, intermediate and delayed effects of radiation exposure enables timely therapeutic interventions. To address whether long noncoding RNAs (lncRNAs) could serve as biomarkers for radiation biodosimetry we performed whole genome transcriptome analysis in a mouse model after whole-body irradiation. Differential lncRNA expression patterns were evaluated at 16, 24 and 48 h postirradiation in total RNA isolated from whole blood of mice exposed to 1, 2, 4,8 and 12 Gy of X rays. Sham-irradiated animals served as controls. Significant alterations in the expression patterns of lncRNAs were observed after different radiation doses at the various time points. We identified several radiation-induced lncRNAs known for DNA damage response as well as immune response. Long noncoding RNA targets of tumor protein 53 (P53), Trp53cor1, Dino, Pvt1 and Tug1 and an upstream regulator of p53, Meg3, were altered in response to radiation. Gm14005 (Morrbid) and Tmevpg1 were regulated by radiation across all time points and doses. These two lncRNAs have important potential as blood-based radiation biomarkers; Gm14005 (Morrbid) has recently been shown to play a key role in inflammatory response, while Tmevpg1 has been implicated in the regulation of interferon gamma. Precise molecular biomarkers, likely involving a diverse group of inducible molecules, will not only enable the development and effective use of medical countermeasures but may also be used to detect and circumvent or mitigate normal tissue injury in cancer radiotherapy.