Molecular Neurobiology

, Volume 51, Issue 1, pp 180–186

Altered Expression of miR-202 in Cerebellum of Multiple-System Atrophy

  • Soon-Tae Lee
  • Kon Chu
  • Keun-Hwa Jung
  • Jae-Jun Ban
  • Woo-Seok Im
  • Hee-Yeon Jo
  • Ji-Hyun Park
  • Ji-Yeon Lim
  • Jung-Won Shin
  • Jangsup Moon
  • Sang Kun Lee
  • Manho Kim
  • Jae-Kyu Roh
Article

DOI: 10.1007/s12035-014-8788-4

Cite this article as:
Lee, S., Chu, K., Jung, K. et al. Mol Neurobiol (2015) 51: 180. doi:10.1007/s12035-014-8788-4

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.

Keywords

Cerebellar degenerationmicroRNAMultiple-system atrophyOct1

Supplementary material

12035_2014_8788_MOESM1_ESM.docx (28 kb)
ESM 1(DOCX 27 kb)
12035_2014_8788_MOESM2_ESM.doc (70 kb)
ESM 2(DOC 70 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • 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. 1.Department of Neurology, Biomedical Research InstituteSeoul National University HospitalSeoulSouth Korea
  2. 2.Program in Neuroscience, Neuroscience Research Institute of SNUMRCSeoul National UniversitySeoulSouth Korea
  3. 3.The Armed Forces Capital HospitalBundang-guSouth Korea
  4. 4.Department of NeurologySeoul National University HospitalJongno-guSouth Korea