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Unraveling the characteristics of microRNA regulation in the developmental and aging process of the human brain

机译：揭示人类大脑发育和衰老过程中microRNA调控的特征

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Background Structure and function of the human brain are subjected to dramatic changes during its development and aging. Studies have demonstrated that microRNAs (miRNAs) play an important role in the regulation of brain development and have a significant impact on brain aging and neurodegeneration. However, the underling molecular mechanisms are not well understood. In general, development and aging are conventionally studied separately, which may not completely address the physiological mechanism over the entire lifespan. Thus, we study the regulatory effect between miRNAs and mRNAs in the developmental and aging process of the human brain by integrating miRNA and mRNA expression profiles throughout the lifetime. Methods In this study, we integrated miRNA and mRNA expression profiles in the human brain across lifespan from the network perspective. First, we chose the age-related miRNAs by polynomial regression models. Second, we constructed the bipartite miRNA-mRNA regulatory network by pair-wise correlation coefficient analysis between miRNA and mRNA expression profiles. At last, we constructed the miRNA-miRNA synergistic network from the miRNA-mRNA network, considering not only the enrichment of target genes but also GO function enrichment of co-regulated target genes. Results We found that the average degree of age-related miRNAs was significantly higher than that of non age-related miRNAs in the miRNA-mRNA regulatory network. The topological features between age-related and non age-related miRNAs were significantly different, and 34 reliable age-related miRNA synergistic modules were identified using Cfinder in the miRNA-miRNA synergistic network. The synergistic regulations of module genes were verified by reviewing miRNA target databases and previous studies. Conclusions Age-related miRNAs play a more important role than non age-related mrRNAs in the developmental and aging process of the human brain. The age-related miRNAs have synergism, which tend to work together as small modules. These results may provide a new insight into the regulation of miRNAs in the developmental and aging process of the human brain.
机译：背景技术人脑的结构和功能在其发展和衰老过程中会发生巨大变化。研究表明，microRNA（miRNA）在调节大脑发育中起重要作用，并且对大脑衰老和神经退行性变有重大影响。但是，对下面的分子机理还没有很好的理解。通常，对发育和衰老的常规研究是分开进行的，这可能无法完全解决整个生命周期中的生理机制。因此，我们通过整合miRNA和mRNA的表达谱，研究了miRNA和mRNA在人脑发育和衰老过程中的调控作用。方法在本研究中，我们从网络角度整合了人类整个生命周期中miRNA和mRNA的表达谱。首先，我们通过多项式回归模型选择了与年龄相关的miRNA。其次，我们通过miRNA和mRNA表达谱之间的成对相关系数分析，构建了两部分miRNA-mRNA调控网络。最后，我们从miRNA-mRNA网络构建了miRNA-miRNA协同网络，不仅要考虑靶基因的富集，还要考虑共同调控靶基因的GO功能富集。结果我们发现在miRNA-mRNA调控网络中，与年龄相关的miRNA的平均程度显着高于非与年龄相关的miRNA。年龄相关和非年龄相关的miRNA之间的拓扑特征显着不同，并且在miRNA-miRNA协同网络中使用Cfinder识别了34个可靠的年龄相关的miRNA协同模块。通过审查miRNA目标数据库和先前的研究，验证了模块基因的协同调控。结论年龄相关的miRNA在人脑的发育和衰老过程中起着比非年龄相关的mrRNA更重要的作用。年龄相关的miRNA具有协同作用，倾向于作为小模块协同工作。这些结果可能为miRNA在人脑发育和衰老过程中的调控提供新的见解。

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