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

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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.

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Acknowledgments

This study was supported by a grant of the Korean Health Technology R&D Project (A121660), Ministry of Health & Welfare, Republic of Korea.

Conflict of Interests

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea

    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

  2. Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea

    Soon-Tae Lee, Kon Chu, Keun-Hwa Jung, Sang Kun Lee & Manho Kim

  3. The Armed Forces Capital Hospital, 177 Saemaul-ro, Bundang-gu, Gyunggi-do, South Korea

    Jae-Kyu Roh

  4. Department of Neurology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea

    Manho Kim

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  1. Soon-Tae Lee
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  2. Kon Chu
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Corresponding authors

Correspondence to Manho Kim or Jae-Kyu Roh.

Additional information

Soon-Tae Lee and Kon Chu contributed equally to this study.

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Lee, ST., Chu, K., Jung, KH. et al. Altered Expression of miR-202 in Cerebellum of Multiple-System Atrophy. Mol Neurobiol 51, 180–186 (2015). https://doi.org/10.1007/s12035-014-8788-4

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  • DOI: https://doi.org/10.1007/s12035-014-8788-4

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