MicroRNA-142 reduces monoamine oxidase A expression and activity in neuronal cells by downregulating SIRT1.
Aberrant expression of microRNAs (miRs) has been implicated in the pathogenesis of several neurodegenerative disorders. In HIV-associated neurocognitive disorders (HAND), miR-142 was found to be upregulated in neurons and myeloid cells in the brain. We investigated the downstream effects of chronic miR-142 upregulation in neuronal cells by comparing gene expression in stable clones of the human neuroblastoma cell line BE(2)M17 expressing miR-142 to controls. Microarray analysis revealed that miR-142 expression led to a reduction in monoamine oxidase (MAO) A mRNA, which was validated by qRT-PCR. In addition to the mRNA, the MAOA protein level and enzyme activity were also reduced. Examination of primary human neurons revealed that miR-142 expression indeed resulted in a downregulation of MAOA protein level. Although MAOA is not a direct target of miR-142, SIRT1, a key transcriptional upregulator of MAOA is, thus miR-142 downregulation of MAOA expression is indirect. MiR-142 induced decrease in MAOA expression and activity may contribute to the changes in dopaminergic neurotransmission reported in HAND.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Amrita Datta
AD
Chaudhuri
Sowmya V
SV
Yelamanchili
Howard S
HS
Fox
D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics*
C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008995:Monoamine Oxidase; D056564:Sirtuin 1