TY - JOUR
T1 - MicroRNA-101 Regulates 6-Hydroxydopamine-Induced Cell Death by Targeting Suppressor/Enhancer Lin-12-Like in SH-SY5Y Cells
AU - Omura, Tomohiro
AU - Nomura, Luna
AU - Watanabe, Ran
AU - Nishiguchi, Hiroki
AU - Yamamoto, Kazuhiro
AU - Imai, Satoshi
AU - Nakagawa, Shunsaku
AU - Itohara, Kotaro
AU - Yonezawa, Atsushi
AU - Nakagawa, Takayuki
AU - Kunimasa, Junichi
AU - Yano, Ikuko
AU - Matsubara, Kazuo
N1 - Funding Information:
This study was supported by JSPS KAKENHI (grant numbers JP 17K08444 and 20K07154).
Publisher Copyright:
Copyright © 2021 Omura, Nomura, Watanabe, Nishiguchi, Yamamoto, Imai, Nakagawa, Itohara, Yonezawa, Nakagawa, Kunimasa, Yano and Matsubara.
PY - 2021/12/9
Y1 - 2021/12/9
N2 - 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.
AB - 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.
KW - endoplasmic reticulum stress (ER stress)
KW - HMG-CoA reductase degradation 1 (HRD1)
KW - microRNA
KW - miR-101
KW - Parkinson’s disease
KW - suppressor/enhancer lin-12-like (SEL1L)
UR - http://www.scopus.com/inward/record.url?scp=85121598571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121598571&partnerID=8YFLogxK
U2 - 10.3389/fnmol.2021.748026
DO - 10.3389/fnmol.2021.748026
M3 - Article
AN - SCOPUS:85121598571
SN - 1662-5099
VL - 14
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 748026
ER -