1. Unraveling the characteristics of microRNA regulation in the developmental and aging process of the human brain
- Author
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Wan Li, Jing Jiang, Xu Jia, Yuehan He, Junjie Lv, Weiming He, Weiguo Li, Xiaoli Qu, Chenchen Feng, Yanyan Zhou, Binbin Chen, Binhua Liang, and Lina Chen
- Subjects
Aging ,Gene regulatory network ,Computational biology ,Biology ,Human brain ,Development ,microRNA ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Gene Regulatory Networks ,Genetics (clinical) ,miRNA ,Mechanism (biology) ,Gene Expression Profiling ,Brain ,Computational Biology ,Human genetics ,Gene expression profiling ,MicroRNAs ,medicine.anatomical_structure ,Synergistic regulation ,DNA microarray ,Function (biology) ,Research Article - Abstract
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.
- Published
- 2013