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Altered Expression of the Long Noncoding RNA NEAT1 in Huntington’s Disease

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Abstract

Huntington’s disease (HD) is a devastating neurodegenerative disease caused by cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene. Growing evidence supports the regulatory functions of long noncoding RNAs (lncRNAs) in the disease process, but little is known about the association between lncRNAs and neuronal death in HD. Here, we evaluated the altered expression profiles of lncRNA in HD by using microarrays. Among dysregulated lncRNAs, we focused on the upregulation of nuclear paraspeckle assembly transcript 1 (NEAT1). Quantitative PCR analysis validated increased NEAT1 levels in the R6/2 mouse brain as well as the human HD postmortem brain. To determine the biological effects of NEAT1 on neuronal survival, neuro2A cells were transfected with the NEAT1 short isoform vector and were subjected to H2O2-induced injury. Subsequently, NEAT1-transfected cells showed increased viability under oxidative stress. Our observations support the notion that NEAT1 upregulation in HD contributes to the neuroprotective mechanism against neuronal injury rather than the pathological process underlying neurodegeneration in HD.

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Acknowledgments

This study was supported by grants from the Korean Health Technology R&D Project (HI14C2348), Ministry of Health and Welfare, Republic of Korea, and the National Research Foundation (NRF) of Korea (2011–0012728). S-T.L was supported by the Seoul National University Hospital Research Fund (04-2014-0730) and Korean Health Technology R&D Project (HI12C1773).

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    Authors and Affiliations

    1. Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea

      Jun-Sang Sunwoo, Soon-Tae Lee, Wooseok Im, Mijung Lee, Jung-Ick Byun, Keun-Hwa Jung, Ki-Young Jung, Sang Kun Lee, Kon Chu & Manho Kim

    2. Program in Neuroscience, College of Medicine, Seoul National University, Seoul, South Korea

      Jun-Sang Sunwoo, Soon-Tae Lee, Wooseok Im, Mijung Lee, Jung-Ick Byun, Keun-Hwa Jung, Ki-Young Jung, Sang Kun Lee, Kon Chu & Manho Kim

    3. Department of Neurology, School of Medicine, Soonchunhyang University, Seoul, South Korea

      Jun-Sang Sunwoo

    4. Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, South Korea

      Jung-Ick Byun

    5. Department of Neurology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, South Korea

      Kyung-Il Park

    6. Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea

      Manho Kim

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    1. Jun-Sang Sunwoo
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    Correspondence to Kon Chu or Manho Kim.

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    Funding

    This study was supported by grants from the Korean Health Technology R&D Project (HI14C2348), Ministry of Health and Welfare, Republic of Korea, and the National Research Foundation (NRF) of Korea (2011–0012728). S-T.L was supported by the Seoul National University Hospital Research Fund (04-2014-0730) and Korean Health Technology R&D Project (HI12C1773).

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    Jun-Sang Sunwoo and Soon-Tae Lee contributed equally to this work.

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    Sunwoo, JS., Lee, ST., Im, W. et al. Altered Expression of the Long Noncoding RNA NEAT1 in Huntington’s Disease. Mol Neurobiol 54, 1577–1586 (2017). https://doi.org/10.1007/s12035-016-9928-9

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