Analysis of miRNA and mRNA expression profiles highlights alterations in ionizing radiation response of human lymphocytes under modeled microgravity.
Analysis of miRNA and mRNA expression profiles highlights alterations in ionizing radiation response of human lymphocytes under modeled microgravity.
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DOI：
10.1371/journal.pone.0031293
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mognato M
中科院分区：
文献类型：
--
作者：
Girardi C;De Pittà C;Casara S;Sales G;Lanfranchi G;Celotti L;Mognato M
电离辐射（IR）对人体细胞是极其有害的，因为对IR的不适当的DNA损伤反应（DDR）可能导致致癌作用的启动。DDR通路中的扰动可以起源于microRNA介导的基因调控功能的改变，microRNA（miRNAs）是充当基因表达的转录后调节因子的小的非编码RNA。在这项研究中，我们深入了解了miRNAs在微重力条件下调节DDR到IR的作用，这是宇航员在太空任务期间经历的失重条件，可能对细胞产生协同作用，增加辐射暴露的风险。我们分析了在正常重力（1g）和模拟微重力（MMG）下培养4和24 h的人外周血淋巴细胞（PBL）在0.2和2Gy γ射线照射后修复期间的miRNA表达谱。我们的研究结果表明，MMG通过减少辐射响应性miRNA的数量来改变辐射PBL的miRNA表达特征。此外，let-7i *、miR-7、miR-7 - 1 *、miR-27 a、miR-144、miR-200 a、miR-598、miR-650通过辐射和MMG的联合作用而去调节。对相同供体PBL进行的miRNA和mRNA表达谱的综合分析鉴定了DDR途径的显著miRNA-mRNA反相关性。基因本体论分析报告，当PBL在1 g中孵育而不是在MMG中孵育时，"对DNA损伤的反应"的生物学类别被富集。此外，一些p53通路的反相关基因在1g和MMG之间显示出不同的表达水平。使用荧光素酶报告基因构建体的功能验证测定证实了源自靶标预测分析的miRNA-mRNA相互作用。总的来说，通过整合转录组和microRNome，我们提供的证据表明，模拟微重力可以影响DNA损伤的反应，在人类PBL的IR。
Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of γ-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of “Response to DNA damage” is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL.
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影响因子：
6.4
作者：
Chintharlapalli, Sudhakar;Papineni, Sabitha;Abdelrahim, Maen;Abudayyeh, Ala;Jutooru, Indira;Chadalapaka, Gayathri;Wu, Fei;Mertens-Talcott, Susanne;Vanderlaag, Kathy;Cho, Sung Dae;Smith, Roger, III;Safe, Stephen
通讯作者：
Safe, Stephen
DOI：
10.1016/0273-1177(86)90074-8
发表时间：
1986-01-01
期刊：
Advances in space research : the official journal of the Committee on Space Research (COSPAR)
影响因子：
--
作者：
Bucker, H;Facius, R;Enge, W
通讯作者：
Enge, W
miR-23a-27a-24-2簇的上调诱导人类胚胎肾细胞中的caspase依赖性和非依赖性凋亡。
影响因子：
3.7
作者：
Chhabra R;Adlakha YK;Hariharan M;Scaria V;Saini N
通讯作者：
Saini N
影响因子：
3.4
作者：
Chaudhry, M. Ahmad
通讯作者：
Chaudhry, M. Ahmad
影响因子：
3.4
作者：
Cromheecke, M;Piers, BA;Hoekstra, HJ
通讯作者：
Hoekstra, HJ