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首页> 外文期刊>Immunity Ageing >Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing
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Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing

机译：全面的环形RNA分析揭示环形RNA100783与CD28相关的慢性CD8（+）T细胞衰老有关

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Background Ageing brings about the gradual deterioration of the immune system, also known as immunosenescence. The role of non-coding circular RNA in immunosenescence is under studied. Using circular RNA microarray data, we assembled Comparison groups (C1, C2, C3 and C4) that allowed us to compare the circular RNA expression profiles between CD28(+)CD8(+) T cells and CD28(-)CD8(+) T cells isolated from healthy elderly or adult control subjects. Using a step-wise biomathematical strategy, the differentially-expressed circRNAs were identified in C1 (CD28(+)CD8(+) vs CD28(-)CD8(+)T cells in the elderly) and C4 (CD28(-)CD8(+)T cells in the elderly vs in the adult), and the commonly-expressed circRNA species from these profiles were optimized as immunosenescence biomarkers. Results Four overlapping upregulated circular RNAs (100550, 100783, 101328 and 102592) expressed in cross-comparison between C1 and C4 were validated using quantitative polymerase chain reaction. Of these, only circular RNA100783 exhibited significant validation. None of the down-regulated circular RNAs were expressed in the C1 and the C4 cross-comparisons. Therefore, we further predicted circular RNA100783-targeted miRNA-gene interactions using online DAVID annotation. The analysis revealed that a circular RNA100783-targeted miRNA-mRNA network may be involved in alternative splicing, the production of splice variants, and in the regulation of phosphoprotein expression. Considering the hypothesis of splicing-related biogenesis of circRNAs, we propose that circular RNA100783 may play a role in phosphoprotein-associated functions duringCD28-related CD8(+) T cell ageing. Conclusions This study is the first to employ circular RNA profiling to investigate circular RNA-micro RNA interactions in ageing human CD8(+)T cell populations and the accompanying loss of CD28 expression. The overlapping expression of circular RNA100783 may represent a novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing and global immunosenescence.
机译：背景老化导致免疫系统逐渐退化，也称为免疫衰老。目前正在研究非编码环状RNA在免疫衰老中的作用。使用环状RNA微阵列数据，我们组装了比较组（C1，C2，C3和C4），这些比较组使我们能够比较CD28（+）CD8（+）T细胞和CD28（-）CD8（+）T细胞之间的环状RNA表达谱从健康的老年人或成人对照组中分离出的细胞。使用逐步生物数学策略，在C1（老年人CD28（+）CD8（+）与CD28（-）CD8（+）T细胞）和C4（CD28（-）CD8（ +）老年人和成年人中的T细胞），并优化了这些图谱中通常表达的circRNA物种作为免疫衰老生物标记。结果使用定量聚合酶链反应验证了在C1和C4之间的交叉比较中表达的四个重叠的上调环状RNA（100550、100783、101328和102592）。其中，仅环状RNA100783表现出显着的验证。在C1和C4交叉比较中均未表达下调的环状RNA。因此，我们使用在线DAVID注释进一步预测了环状RNA100783靶向的miRNA-基因相互作用。分析显示，靶向环状RNA100783的miRNA-mRNA网络可能参与选择性剪接，剪接变体的产生以及磷蛋白表达的调节。考虑到circRNA的剪接相关生物发生的假设，我们建议在CD28相关CD8（+）T细胞老化期间，环状RNA100783可能在磷蛋白相关功能中起作用。结论这项研究是第一个使用环状RNA分析来研究衰老的人类CD8（+）T细胞群体中环状RNA-微小RNA相互作用以及随之而来的CD28表达损失的研究。环状RNA100783的重叠表达可能代表一种新型的生物标志物，用于纵向跟踪CD28相关的CD8（+）T细胞衰老和整体免疫衰老。

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