{"title":"揭示帕金森病细胞模型中 miR-101-3p 对 ZNF746 的调控作用:治疗靶点的意义","authors":"Maryam Mahmoudian Esfahani , Maryam Mostashfi , Shiva Vaheb Hosseinabadi , Motahare-Sadat Hashemi , Maryam Peymani , Dina Zohrabi , Seyed Abdolhamid Angaji , Mohammad Hossein Nasr-Esfahani , Kamran Ghaedi","doi":"10.1016/j.neures.2023.12.001","DOIUrl":null,"url":null,"abstract":"<div><p>In this study, we explored the regulatory role of microRNA miR-101-3p on the zinc finger protein 746 (ZNF746), also known as PARIS, which is implicated in both sporadic and familial forms of Parkinson's disease. In a Parkinson's disease cell model, utilizing SH-SY5Y cells treated with 1-methyl-4-phenylpyridine (MPP+), we observed that miR-101–3p was downregulated, while ZNF746 was upregulated. To investigate the direct impact of miR-101-3p on ZNF746, our team conducted overexpression experiments, successfully reversing ZNF746's expression at both the mRNA and protein levels, as confirmed through quantitative PCR and western blotting. We also performed luciferase assays, providing compelling evidence that ZNF746 is a direct target of miR-101-3p. Additionally, we noted that miR-101-3p overexpression resulted in increased expression of PGC1α, a gene targeted by ZNF746. Functionally, we assessed the implications of miR-101-3p overexpression through MTS assays and flow cytometry, revealing significant promotion of cell viability, inhibition of ROS production, and reduced apoptosis in the Parkinson's disease cell model. In conclusion, this study highlights the role of miR-101-3p in regulating ZNF746 expression and suggests its potential as a therapeutic target for Parkinson's disease. These findings provide valuable molecular insights that could pave the way for innovative treatment strategies in combating this debilitating neurodegenerative disorder.</p></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"203 ","pages":"Pages 18-27"},"PeriodicalIF":2.4000,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016801022300216X/pdfft?md5=1f81dcc751f3c553fd4d1c78d722336f&pid=1-s2.0-S016801022300216X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson's disease cell model: Implications for therapeutic targeting\",\"authors\":\"Maryam Mahmoudian Esfahani , Maryam Mostashfi , Shiva Vaheb Hosseinabadi , Motahare-Sadat Hashemi , Maryam Peymani , Dina Zohrabi , Seyed Abdolhamid Angaji , Mohammad Hossein Nasr-Esfahani , Kamran Ghaedi\",\"doi\":\"10.1016/j.neures.2023.12.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In this study, we explored the regulatory role of microRNA miR-101-3p on the zinc finger protein 746 (ZNF746), also known as PARIS, which is implicated in both sporadic and familial forms of Parkinson's disease. In a Parkinson's disease cell model, utilizing SH-SY5Y cells treated with 1-methyl-4-phenylpyridine (MPP+), we observed that miR-101–3p was downregulated, while ZNF746 was upregulated. To investigate the direct impact of miR-101-3p on ZNF746, our team conducted overexpression experiments, successfully reversing ZNF746's expression at both the mRNA and protein levels, as confirmed through quantitative PCR and western blotting. We also performed luciferase assays, providing compelling evidence that ZNF746 is a direct target of miR-101-3p. Additionally, we noted that miR-101-3p overexpression resulted in increased expression of PGC1α, a gene targeted by ZNF746. Functionally, we assessed the implications of miR-101-3p overexpression through MTS assays and flow cytometry, revealing significant promotion of cell viability, inhibition of ROS production, and reduced apoptosis in the Parkinson's disease cell model. In conclusion, this study highlights the role of miR-101-3p in regulating ZNF746 expression and suggests its potential as a therapeutic target for Parkinson's disease. These findings provide valuable molecular insights that could pave the way for innovative treatment strategies in combating this debilitating neurodegenerative disorder.</p></div>\",\"PeriodicalId\":19146,\"journal\":{\"name\":\"Neuroscience Research\",\"volume\":\"203 \",\"pages\":\"Pages 18-27\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2023-12-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S016801022300216X/pdfft?md5=1f81dcc751f3c553fd4d1c78d722336f&pid=1-s2.0-S016801022300216X-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroscience Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S016801022300216X\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S016801022300216X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson's disease cell model: Implications for therapeutic targeting
In this study, we explored the regulatory role of microRNA miR-101-3p on the zinc finger protein 746 (ZNF746), also known as PARIS, which is implicated in both sporadic and familial forms of Parkinson's disease. In a Parkinson's disease cell model, utilizing SH-SY5Y cells treated with 1-methyl-4-phenylpyridine (MPP+), we observed that miR-101–3p was downregulated, while ZNF746 was upregulated. To investigate the direct impact of miR-101-3p on ZNF746, our team conducted overexpression experiments, successfully reversing ZNF746's expression at both the mRNA and protein levels, as confirmed through quantitative PCR and western blotting. We also performed luciferase assays, providing compelling evidence that ZNF746 is a direct target of miR-101-3p. Additionally, we noted that miR-101-3p overexpression resulted in increased expression of PGC1α, a gene targeted by ZNF746. Functionally, we assessed the implications of miR-101-3p overexpression through MTS assays and flow cytometry, revealing significant promotion of cell viability, inhibition of ROS production, and reduced apoptosis in the Parkinson's disease cell model. In conclusion, this study highlights the role of miR-101-3p in regulating ZNF746 expression and suggests its potential as a therapeutic target for Parkinson's disease. These findings provide valuable molecular insights that could pave the way for innovative treatment strategies in combating this debilitating neurodegenerative disorder.
期刊介绍:
The international journal publishing original full-length research articles, short communications, technical notes, and reviews on all aspects of neuroscience
Neuroscience Research is an international journal for high quality articles in all branches of neuroscience, from the molecular to the behavioral levels. The journal is published in collaboration with the Japan Neuroscience Society and is open to all contributors in the world.