Email updates

Keep up to date with the latest news and content from BMC Medical Genomics and BioMed Central.

Open Access Highly Accessed Research article

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

Weiguo Li1, Lina Chen1*, Wan Li1, Xiaoli Qu1, Weiming He2, Yuehan He1, Chenchen Feng1, Xu Jia1, Yanyan Zhou1, Junjie Lv1, Binhua Liang3, Binbin Chen1 and Jing Jiang1

Author Affiliations

1 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province, China

2 Institute of Opto-electronics, Harbin Institute of Technology, Harbin, Heilongjiang Province, China

3 National Microbology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada

For all author emails, please log on.

BMC Medical Genomics 2013, 6:55  doi:10.1186/1755-8794-6-55

Published: 9 December 2013

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.

Keywords:
Human brain; Development; Aging; miRNA; Synergistic regulation