title: Discovering dysfunction of multiple microRNAs cooperation in disease by a conserved microRNA co-expression network.
abstract: MicroRNAs, a new class of key regulators of gene expression, have been shown to be involved in diverse biological processes and linked to many human diseases. To elucidate miRNA function from a global perspective, we constructed a conserved miRNA co-expression network by integrating multiple human and mouse miRNA expression data. We found that these conserved co-expressed miRNA pairs tend to reside in close genomic proximity, belong to common families, share common transcription factors, and regulate common biological processes by targeting common components of those processes based on miRNA targets and miRNA knockout/transfection expression data, suggesting their strong functional associations. We also identified several co-expressed miRNA sub-networks. Our analysis reveals that many miRNAs in the same sub-network are associated with the same diseases. By mapping known disease miRNAs to the network, we identified three cancer-related miRNA sub-networks. Functional analyses based on targets and miRNA knockout/transfection data consistently show that these sub-networks are significantly involved in cancer-related biological processes, such as apoptosis and cell cycle. Our results imply that multiple co-expressed miRNAs can cooperatively regulate a given biological process by targeting common components of that process, and the pathogenesis of disease may be associated with the abnormality of multiple functionally cooperative miRNAs rather than individual miRNAs. In addition, many of these co-expression relationships provide strong evidence for the involvement of new miRNAs in important biological processes, such as apoptosis, differentiation and cell cycle, indicating their potential disease links.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Chaohan
authors.initials: C
authors.lastname: Xu
authors.forename: Jinxia
authors.initials: J
authors.lastname: Guan
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ping
authors.forename: Huihui
authors.initials: H
authors.lastname: Fan
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Li
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhao
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D016000:Cluster Analysis; D017124:Conserved Sequence; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D023281:Genomics; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011336:Probability; D014176:Protein Biosynthesis; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs