title: Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation.
abstract: Although microRNAs are being extensively studied for their involvement in cancer and development, little is known about their roles in Alzheimer's disease (AD). In this study, we used microarrays for the first joint profiling and analysis of miRNAs and mRNAs expression in brain cortex from AD and age-matched control subjects. These data provided the unique opportunity to study the relationship between miRNA and mRNA expression in normal and AD brains. Using a non-parametric analysis, we showed that the levels of many miRNAs can be either positively or negatively correlated with those of their target mRNAs. Comparative analysis with independent cancer datasets showed that such miRNA-mRNA expression correlations are not static, but rather context-dependent. Subsequently, we identified a large set of miRNA-mRNA associations that are changed in AD versus control, highlighting AD-specific changes in the miRNA regulatory system. Our results demonstrate a robust relationship between the levels of miRNAs and those of their targets in the brain. This has implications in the study of the molecular pathology of AD, as well as miRNA biology in general.
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Juan
authors.initials: J
authors.lastname: Nunez-Iglesias
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Liu
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
authors.forename: Xianghong Jasmine
authors.initials: XJ
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001499:Bayes Theorem; D001921:Brain / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger