Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathology
Background: Kruppel-like factor 9 (KLF9) plays a key role as an inducer of cellular oxidative stress in the modulation of cell death and in oxidant-dependent tissue injury. Our previous study indicated that lncRNA-T199678 (T199678) affected the expression of KLF9 in an α-synuclein (α-syn) induced ce...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923022001277 |
| _version_ | 1797367846111543296 |
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| author | Danyu Lin Yao Li Kaixun Huang Ying Chen Xiuna Jing Yanran Liang Lulu Bu Sudan Peng Shaowei Zeng Tetsuya Asakawa Enxiang Tao |
| author_facet | Danyu Lin Yao Li Kaixun Huang Ying Chen Xiuna Jing Yanran Liang Lulu Bu Sudan Peng Shaowei Zeng Tetsuya Asakawa Enxiang Tao |
| author_sort | Danyu Lin |
| collection | DOAJ |
| description | Background: Kruppel-like factor 9 (KLF9) plays a key role as an inducer of cellular oxidative stress in the modulation of cell death and in oxidant-dependent tissue injury. Our previous study indicated that lncRNA-T199678 (T199678) affected the expression of KLF9 in an α-synuclein (α-syn) induced cellular model. However, the roles of interactions among α-syn, T199678, KLF9 and related microRNAs (miRNAs) in the Parkinson’s disease (PD)-related α-syn pathology are unclear and were therefore investigated in this study. Methods: An α-syn-injected mouse model and an α-syn exposed SY-SH5Y cellular model were used in this study. We confirmed the utility of these established models with morphological and behavioral methods. We checked how expression of T199678 and KLF9 were affected by α-syn and demonstrated their interaction by fluorescence in situ hybridization (FISH) staining and western blots. We analyzed expression in ROS+ cells by immunohistochemistry. Finally, we obtained seven miRNAs through bioinformatic analysis simultaneously affected by T199678 and α-syn and verified these with RT-PCR. Results: We found that expression of KLF9 was regulated by T199678, whereas expression of T199678 was not affected by KLF9 in the α-syn exposed SY-SH5Y cells. These findings suggest that KLF9 is the downstream gene regulated by T199678, whereas miR-519–3p may play a contributing role. We also confirmed that α-syn injection upregulated the expression of ROS, which could be downregulated by upregulation of T199678, indicating an anti-oxidative role of T199678 in the α-syn-related mechanisms. Conclusions: Our results indicate the existence of a potential α-syn/T199678/miR-519–3p /KLF9 pathway in PD-related α-syn pathology. This pathway might explain oxidative stress processes in α-syn-related mechanisms, which requires further verification. |
| first_indexed | 2024-03-08T17:22:58Z |
| format | Article |
| id | doaj.art-b1b28910ebae450d8260245a8b9ddfa6 |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-08T17:22:58Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-b1b28910ebae450d8260245a8b9ddfa62024-01-03T04:11:24ZengElsevierBrain Research Bulletin1873-27472022-08-011865061Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathologyDanyu Lin0Yao Li1Kaixun Huang2Ying Chen3Xiuna Jing4Yanran Liang5Lulu Bu6Sudan Peng7Shaowei Zeng8Tetsuya Asakawa9Enxiang Tao10Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, ChinaDepartment of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China; Correspondence to: Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shennanzhong Road 3025, Shenzhen, Guangdong 518033, China.Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China; Department of Neurology, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510120, China; Correspondence to: Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shennanzhong Road 3025, Shenzhen, Guangdong 518033, China.Background: Kruppel-like factor 9 (KLF9) plays a key role as an inducer of cellular oxidative stress in the modulation of cell death and in oxidant-dependent tissue injury. Our previous study indicated that lncRNA-T199678 (T199678) affected the expression of KLF9 in an α-synuclein (α-syn) induced cellular model. However, the roles of interactions among α-syn, T199678, KLF9 and related microRNAs (miRNAs) in the Parkinson’s disease (PD)-related α-syn pathology are unclear and were therefore investigated in this study. Methods: An α-syn-injected mouse model and an α-syn exposed SY-SH5Y cellular model were used in this study. We confirmed the utility of these established models with morphological and behavioral methods. We checked how expression of T199678 and KLF9 were affected by α-syn and demonstrated their interaction by fluorescence in situ hybridization (FISH) staining and western blots. We analyzed expression in ROS+ cells by immunohistochemistry. Finally, we obtained seven miRNAs through bioinformatic analysis simultaneously affected by T199678 and α-syn and verified these with RT-PCR. Results: We found that expression of KLF9 was regulated by T199678, whereas expression of T199678 was not affected by KLF9 in the α-syn exposed SY-SH5Y cells. These findings suggest that KLF9 is the downstream gene regulated by T199678, whereas miR-519–3p may play a contributing role. We also confirmed that α-syn injection upregulated the expression of ROS, which could be downregulated by upregulation of T199678, indicating an anti-oxidative role of T199678 in the α-syn-related mechanisms. Conclusions: Our results indicate the existence of a potential α-syn/T199678/miR-519–3p /KLF9 pathway in PD-related α-syn pathology. This pathway might explain oxidative stress processes in α-syn-related mechanisms, which requires further verification.http://www.sciencedirect.com/science/article/pii/S0361923022001277α-Synucleinα-Syn/T199678/miR-519–3p /KLF9 pathwayKLF9LncRNA-T199678MiR-519–3pParkinson’s disease |
| spellingShingle | Danyu Lin Yao Li Kaixun Huang Ying Chen Xiuna Jing Yanran Liang Lulu Bu Sudan Peng Shaowei Zeng Tetsuya Asakawa Enxiang Tao Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathology Brain Research Bulletin α-Synuclein α-Syn/T199678/miR-519–3p /KLF9 pathway KLF9 LncRNA-T199678 MiR-519–3p Parkinson’s disease |
| title | Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathology |
| title_full | Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathology |
| title_fullStr | Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathology |
| title_full_unstemmed | Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathology |
| title_short | Exploration of the α-syn/T199678/miR-519–3p/KLF9 pathway in a PD-related α-syn pathology |
| title_sort | exploration of the α syn t199678 mir 519 3p klf9 pathway in a pd related α syn pathology |
| topic | α-Synuclein α-Syn/T199678/miR-519–3p /KLF9 pathway KLF9 LncRNA-T199678 MiR-519–3p Parkinson’s disease |
| url | http://www.sciencedirect.com/science/article/pii/S0361923022001277 |
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