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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |