Dysregulation of miRNA 181b in the temporal cortex in schizophrenia.
Analysis of global microRNA (miRNA) expression in postmortem cortical grey matter from the superior temporal gyrus, revealed significant up-regulation of miR-181b expression in schizophrenia. This finding was supported by quantitative real-time RT-PCR analysis of miRNA expression in a cohort of 21 matched pairs of schizophrenia and non-psychiatric controls. The implications of this finding are substantial, as this miRNA is predicted to regulate many target genes with potential significance to the development of schizophrenia. They include the calcium sensor gene visinin-like 1 (VSNL1) and the ionotropic AMPA glutamate receptor subunit (GRIA2), which were found to be down-regulated in the same cortical tissue from the schizophrenia group. Both of these genes were also suppressed in miR-181b transfected cells and shown to contain functional miR-181b miRNA recognition elements by reporter gene assay. This study suggests altered miRNA levels could be a significant factor in the dysregulation of cortical gene expression in schizophrenia.
Beveridge
Natalie J
NJ
Schizophrenia Research Institute, Sydney, NSW 2006, Australia.
Tooney
Paul A
PA
Carroll
Adam P
AP
Gardiner
Erin
E
Bowden
Nikola
N
Scott
Rodney J
RJ
Tran
Nham
N
Dedova
Irina
I
Cairns
Murray J
MJ
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051596:Neurocalcin / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism; D014162:Transfection
D035683:MicroRNAs; D051596:Neurocalcin; D018091:Receptors, AMPA; C496688:VSNL1 protein, human; C104722:glutamate receptor ionotropic, AMPA 2