PMID- 35654261 OWN - NLM STAT- MEDLINE DCOM- 20220629 LR - 20220719 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 186 DP - 2022 Aug TI - Exploration of the alpha-syn/T199678/miR-519-3p/KLF9 pathway in a PD-related alpha-syn pathology. PG - 50-61 LID - S0361-9230(22)00127-7 [pii] LID - 10.1016/j.brainresbull.2022.05.012 [doi] AB - 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 alpha-synuclein (alpha-syn) induced cellular model. However, the roles of interactions among alpha-syn, T199678, KLF9 and related microRNAs (miRNAs) in the Parkinson's disease (PD)-related alpha-syn pathology are unclear and were therefore investigated in this study. METHODS: An alpha-syn-injected mouse model and an alpha-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 alpha-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 alpha-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 alpha-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 alpha-syn injection upregulated the expression of ROS, which could be downregulated by upregulation of T199678, indicating an anti-oxidative role of T199678 in the alpha-syn-related mechanisms. CONCLUSIONS: Our results indicate the existence of a potential alpha-syn/T199678/miR-519-3p /KLF9 pathway in PD-related alpha-syn pathology. This pathway might explain oxidative stress processes in alpha-syn-related mechanisms, which requires further verification. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Lin, Danyu AU - Lin D AD - Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China. FAU - Li, Yao AU - Li Y AD - 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. FAU - Huang, Kaixun AU - Huang K AD - Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China. FAU - Chen, Ying AU - Chen Y AD - 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. FAU - Jing, Xiuna AU - Jing X AD - 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. FAU - Liang, Yanran AU - Liang Y AD - 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. FAU - Bu, Lulu AU - Bu L AD - 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. FAU - Peng, Sudan AU - Peng S AD - 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. FAU - Zeng, Shaowei AU - Zeng S AD - 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. FAU - Asakawa, Tetsuya AU - Asakawa T AD - Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China. Electronic address: asakawat1971@gmail.com. FAU - Tao, Enxiang AU - Tao E AD - 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. Electronic address: taoex@mail.sysu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220530 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Klf9 protein, mouse) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (MicroRNAs) RN - 0 (Reactive Oxygen Species) RN - 0 (Snca protein, mouse) RN - 0 (alpha-Synuclein) SB - IM MH - Animals MH - In Situ Hybridization, Fluorescence MH - Kruppel-Like Transcription Factors/metabolism MH - Mice MH - *MicroRNAs/genetics/metabolism MH - *Parkinson Disease/metabolism MH - Reactive Oxygen Species MH - alpha-Synuclein/metabolism OTO - NOTNLM OT - KLF9 OT - LncRNA-T199678 OT - MiR-519-3p OT - Parkinson's disease OT - alpha-Syn/T199678/miR-519-3p /KLF9 pathway OT - alpha-Synuclein EDAT- 2022/06/03 06:00 MHDA- 2022/06/30 06:00 CRDT- 2022/06/02 19:25 PHST- 2021/11/10 00:00 [received] PHST- 2022/05/17 00:00 [revised] PHST- 2022/05/25 00:00 [accepted] PHST- 2022/06/03 06:00 [pubmed] PHST- 2022/06/30 06:00 [medline] PHST- 2022/06/02 19:25 [entrez] AID - S0361-9230(22)00127-7 [pii] AID - 10.1016/j.brainresbull.2022.05.012 [doi] PST - ppublish SO - Brain Res Bull. 2022 Aug;186:50-61. doi: 10.1016/j.brainresbull.2022.05.012. Epub 2022 May 30.