title: Altered expression of miR-202 in cerebellum of multiple-system atrophy.
abstract: Cerebellar degeneration is a devastating manifestation of cerebellar-type multiple-system atrophy (MSA), a rapidly progressive neurodegenerative disease, and the exact pathogenesis is unknown. Here, we examined the expression of micro-RNAs (miRNAs), which are short noncoding RNAs, in the cerebellum of MSA and the key target genes. miRNA microarray found 11 miRNAs with significantly different expression in MSA cerebellum compared to cerebellum from age-, sex-, and postmortem interval-matched controls. miR-202 was the most upregulated in the MSA samples. In silico analysis, followed by target gene luciferase assay, in vitro transfection, and Western blotting in human samples showed that miR-202 downregulates Oct1 (Pou2f1), a transcription factor expressed in cerebellar Purkinje cells. Transfection of Neuro-2a cells with miR-202 enhanced oxidative stress-induced cell death, and an antagomir to miR-202 inhibited this effect of miR-202. This study provides novel insight into the role of miRNA in cerebellar degeneration and suggests that miR-202 is a key miRNA mediating the pathogenesis of MSA.
authors: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors: Soon-Tae
authors: ST
authors: Lee
authors: Kon
authors: K
authors: Chu
authors: Keun-Hwa
authors: KH
authors: Jung
authors: Jae-Jun
authors: JJ
authors: Ban
authors: Woo-Seok
authors: WS
authors: Im
authors: Hee-Yeon
authors: HY
authors: Jo
authors: Ji-Hyun
authors: JH
authors: Park
authors: Ji-Yeon
authors: JY
authors: Lim
authors: Jung-Won
authors: JW
authors: Shin
authors: Jangsup
authors: J
authors: Moon
authors: Sang Kun
authors: SK
authors: Lee
authors: Manho
authors: M
authors: Kim
authors: Jae-Kyu
authors: JK
authors: Roh
mesh_terms: D000368:Aged; D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D019578:Multiple System Atrophy / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D050811:Octamer Transcription Factor-1 / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C569392:MIRN202 microRNA, human; C583892:MIRN202 microRNA, mouse; D035683:MicroRNAs; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human