Cargando…

MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells

Endoplasmic reticulum (ER) stress has been reported as a cause of Parkinson’s disease (PD). We have previously reported that the ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) and its stabilizing factor suppressor/enhancer lin-12-like (SEL1L) participate in the ER stress. In addition, we re...

Descripción completa

Detalles Bibliográficos
Autores principales: Omura, Tomohiro, Nomura, Luna, Watanabe, Ran, Nishiguchi, Hiroki, Yamamoto, Kazuhiro, Imai, Satoshi, Nakagawa, Shunsaku, Itohara, Kotaro, Yonezawa, Atsushi, Nakagawa, Takayuki, Kunimasa, Junichi, Yano, Ikuko, Matsubara, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695805/
https://www.ncbi.nlm.nih.gov/pubmed/34955743
http://dx.doi.org/10.3389/fnmol.2021.748026
_version_ 1784619661437960192
author Omura, Tomohiro
Nomura, Luna
Watanabe, Ran
Nishiguchi, Hiroki
Yamamoto, Kazuhiro
Imai, Satoshi
Nakagawa, Shunsaku
Itohara, Kotaro
Yonezawa, Atsushi
Nakagawa, Takayuki
Kunimasa, Junichi
Yano, Ikuko
Matsubara, Kazuo
author_facet Omura, Tomohiro
Nomura, Luna
Watanabe, Ran
Nishiguchi, Hiroki
Yamamoto, Kazuhiro
Imai, Satoshi
Nakagawa, Shunsaku
Itohara, Kotaro
Yonezawa, Atsushi
Nakagawa, Takayuki
Kunimasa, Junichi
Yano, Ikuko
Matsubara, Kazuo
author_sort Omura, Tomohiro
collection PubMed
description Endoplasmic reticulum (ER) stress has been reported as a cause of Parkinson’s disease (PD). We have previously reported that the ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) and its stabilizing factor suppressor/enhancer lin-12-like (SEL1L) participate in the ER stress. In addition, we recently demonstrated that neuronal cell death is enhanced in the cellular PD model when SEL1L expression is suppressed compared with cell death when HRD1 expression is suppressed. This finding suggests that SEL1L is a critical key molecule in the strategy for PD therapy. Thus, investigation into whether microRNAs (miRNAs) regulate SEL1L expression in neurons should be interesting because relationships between miRNAs and the development of neurological diseases such as PD have been reported in recent years. In this study, using miRNA databases and previous reports, we searched for miRNAs that could regulate SEL1L expression and examined the effects of this regulation on cell death in PD models created by 6-hydroxydopamine (6-OHDA). Five miRNAs were identified as candidate miRNAs that could modulate SEL1L expression. Next, SH-SY5Y cells were exposed to 6-OHDA, following which miR-101 expression was found to be inversely correlated with SEL1L expression. Therefore, we selected miR-101 as a candidate miRNA for SEL1L modulation. We confirmed that miR-101 directly targets the SEL1L 3′ untranslated region, and an miR-101 mimic suppressed the 6-OHDA–induced increase in SEL1L expression and enhanced cell death. Furthermore, an miR-101 inhibitor suppressed this response. These results suggest that miR-101 regulates SEL1L expression and may serve as a new target for PD therapy.
format Online
Article
Text
id pubmed-8695805
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86958052021-12-24 MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells Omura, Tomohiro Nomura, Luna Watanabe, Ran Nishiguchi, Hiroki Yamamoto, Kazuhiro Imai, Satoshi Nakagawa, Shunsaku Itohara, Kotaro Yonezawa, Atsushi Nakagawa, Takayuki Kunimasa, Junichi Yano, Ikuko Matsubara, Kazuo Front Mol Neurosci Molecular Neuroscience Endoplasmic reticulum (ER) stress has been reported as a cause of Parkinson’s disease (PD). We have previously reported that the ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) and its stabilizing factor suppressor/enhancer lin-12-like (SEL1L) participate in the ER stress. In addition, we recently demonstrated that neuronal cell death is enhanced in the cellular PD model when SEL1L expression is suppressed compared with cell death when HRD1 expression is suppressed. This finding suggests that SEL1L is a critical key molecule in the strategy for PD therapy. Thus, investigation into whether microRNAs (miRNAs) regulate SEL1L expression in neurons should be interesting because relationships between miRNAs and the development of neurological diseases such as PD have been reported in recent years. In this study, using miRNA databases and previous reports, we searched for miRNAs that could regulate SEL1L expression and examined the effects of this regulation on cell death in PD models created by 6-hydroxydopamine (6-OHDA). Five miRNAs were identified as candidate miRNAs that could modulate SEL1L expression. Next, SH-SY5Y cells were exposed to 6-OHDA, following which miR-101 expression was found to be inversely correlated with SEL1L expression. Therefore, we selected miR-101 as a candidate miRNA for SEL1L modulation. We confirmed that miR-101 directly targets the SEL1L 3′ untranslated region, and an miR-101 mimic suppressed the 6-OHDA–induced increase in SEL1L expression and enhanced cell death. Furthermore, an miR-101 inhibitor suppressed this response. These results suggest that miR-101 regulates SEL1L expression and may serve as a new target for PD therapy. Frontiers Media S.A. 2021-12-09 /pmc/articles/PMC8695805/ /pubmed/34955743 http://dx.doi.org/10.3389/fnmol.2021.748026 Text en Copyright © 2021 Omura, Nomura, Watanabe, Nishiguchi, Yamamoto, Imai, Nakagawa, Itohara, Yonezawa, Nakagawa, Kunimasa, Yano and Matsubara. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Omura, Tomohiro
Nomura, Luna
Watanabe, Ran
Nishiguchi, Hiroki
Yamamoto, Kazuhiro
Imai, Satoshi
Nakagawa, Shunsaku
Itohara, Kotaro
Yonezawa, Atsushi
Nakagawa, Takayuki
Kunimasa, Junichi
Yano, Ikuko
Matsubara, Kazuo
MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells
title MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells
title_full MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells
title_fullStr MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells
title_full_unstemmed MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells
title_short MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells
title_sort microrna-101 regulates 6-hydroxydopamine-induced cell death by targeting suppressor/enhancer lin-12-like in sh-sy5y cells
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695805/
https://www.ncbi.nlm.nih.gov/pubmed/34955743
http://dx.doi.org/10.3389/fnmol.2021.748026
work_keys_str_mv AT omuratomohiro microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT nomuraluna microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT watanaberan microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT nishiguchihiroki microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT yamamotokazuhiro microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT imaisatoshi microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT nakagawashunsaku microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT itoharakotaro microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT yonezawaatsushi microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT nakagawatakayuki microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT kunimasajunichi microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT yanoikuko microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells
AT matsubarakazuo microrna101regulates6hydroxydopamineinducedcelldeathbytargetingsuppressorenhancerlin12likeinshsy5ycells