title: Unraveling the characteristics of microRNA regulation in the developmental and aging process of the human brain.
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 underlining 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.
authors: Weiguo
authors: W
authors: Li
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province, China. chenlina@ems.hrbmu.edu.cn.
authors: Lina
authors: L
authors: Chen
authors: Wan
authors: W
authors: Li
authors: Xiaoli
authors: X
authors: Qu
authors: Weiming
authors: W
authors: He
authors: Yuehan
authors: Y
authors: He
authors: Chenchen
authors: C
authors: Feng
authors: Xu
authors: X
authors: Jia
authors: Yanyan
authors: Y
authors: Zhou
authors: Junjie
authors: J
authors: Lv
authors: Binhua
authors: B
authors: Liang
authors: Binbin
authors: B
authors: Chen
authors: Jing
authors: J
authors: Jiang
mesh_terms: D000375:Aging / Q000235:genetics*; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D019295:Computational Biology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs