MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders.
MicroRNAs (miRNAs) are a large family of small non-coding RNAs which negatively control gene expression at both the mRNA and protein levels. The number of miRNAs identified is growing rapidly and approximately one-third is expressed in the brain where they have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. Here we investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N = 35) and bipolar disorder (BP, N = 35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as being differentially expressed between cases and controls, 7 dysregulated in SZ and 15 in BP. Using in silico target gene prediction programs, the 22miRNAs were found to target brain specific genes contained within networks overrepresented for neurodevelopment, behavior, and SZ and BP disease development. In an initial attempt to corroborate some of these predictions, we investigated the extent of correlation between the expressions of hsa-mir-34a, -132 and -212 and their predicted gene targets. mRNA expression of tyrosine hydroxylase (TH), phosphogluconate dehydrogenase (PGD) and metabotropic glutamate receptor 3 (GRM3) was measured in the SMRI sample. Hsa-miR-132 and -212 were negatively correlated with TH (p = 0.0001 and 0.0017) and with PGD (p = 0.0054 and 0.017, respectively).
Kim
Albert H
AH
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0424, USA.
Reimers
Mark
M
Maher
Brion
B
Williamson
Vernell
V
McMichael
Omari
O
McClay
Joseph L
JL
van den Oord
Edwin J C G
EJ
Riley
Brien P
BP
Kendler
Kenneth S
KS
Vladimirov
Vladimir I
VI
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D011457:Prostaglandins D / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
C547077:MIRN132 microRNA, human; C551411:MIRN212 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D011457:Prostaglandins D; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; D014446:Tyrosine 3-Monooxygenase