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Altered Expression of miR-202 in Cerebellum of Multiple-System Atrophy
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  • 作者:Soon-Tae Lee (1) (2)
    Kon Chu (1) (2)
    Keun-Hwa Jung (1) (2)
    Jae-Jun Ban (1)
    Woo-Seok Im (1)
    Hee-Yeon Jo (1)
    Ji-Hyun Park (1)
    Ji-Yeon Lim (1)
    Jung-Won Shin (1)
    Jangsup Moon (1)
    Sang Kun Lee (1) (2)
    Manho Kim (1) (2) (4)
    Jae-Kyu Roh (1) (3)

    1. Department of Neurology
    ; Biomedical Research Institute ; Seoul National University Hospital ; Seoul ; South Korea
    2. Program in Neuroscience
    ; Neuroscience Research Institute of SNUMRC ; Seoul National University ; Seoul ; South Korea
    4. Department of Neurology
    ; Seoul National University Hospital ; 101 Daehak-ro ; Jongno-gu ; Seoul ; 110-744 ; South Korea
    3. The Armed Forces Capital Hospital
    ; 177 Saemaul-ro ; Bundang-gu ; Gyunggi-do ; South Korea
  • 关键词:Cerebellar degeneration ; microRNA ; Multiple ; system atrophy ; Oct1
  • 刊名:Molecular Neurobiology
  • 出版年:2015
  • 出版时间:February 2015
  • 年:2015
  • 卷:51
  • 期:1
  • 页码:180-186
  • 全文大小:573 KB
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  • 刊物主题:Neurosciences; Neurobiology; Cell Biology; Neurology;
  • 出版者:Springer US
  • ISSN:1559-1182
文摘
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.

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