PMID- 35973363 OWN - NLM STAT- MEDLINE DCOM- 20220926 LR - 20220928 IS - 2213-2317 (Electronic) IS - 2213-2317 (Linking) VI - 56 DP - 2022 Oct TI - CircSV2b participates in oxidative stress regulation through miR-5107-5p-Foxk1-Akt1 axis in Parkinson's disease. PG - 102430 LID - S2213-2317(22)00202-6 [pii] LID - 10.1016/j.redox.2022.102430 [doi] LID - 102430 AB - As a novel type of non-coding RNAs, covalently closed circular RNAs (circRNAs) are ubiquitously expressed in eukaryotes. Emerging studies have indicated that dysregulation of circRNAs was related to neurological diseases. However, the biogenesis, regulation, function, and mechanism of circRNAs in Parkinson's disease (PD) remain largely unclear. In this study, thirty-three differentially expressed circRNAs (DECs) were detected by RNA-sequencing between the MPTP-induced PD mice model and the wild-type mice. Quantitative real-time PCR was used to determine the RNA level of DECs in the striatum (STR), substantia nigra pars compacta (SNpc), and serum exosomes, and it was found that circSV2b was downregulated in PD mice. Then, functional experiments in vivo were employed to explore the effect of circSV2b in PD. For the mechanism study, dual-luciferase reporter, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), RNA pull-down, gene editing, and CUT & Tag were performed in vitro to confirm that circSV2b directly sponged miR-5107-5p and alleviated the suppression of the expression of the target gene Foxk1, and then positively regulated Akt1 transcription. In vivo, the mechanistic analysis demonstrated that circSV2b overexpression resisted oxidative stress damage through the ceRNA-Akt1 axis in PD models. Taken together, these findings suggested that the miR-5107-5p-Foxk1-Akt1 axis might serve as a key target of circSV2b overexpression in PD treatment, and highlighted the significant change of circSV2b in serum exosomes. Therefore, circSV2b might be a novel biomarker for the diagnosis and treatment of PD. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Cheng, Quancheng AU - Cheng Q AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Wang, Jianwei AU - Wang J AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Li, Man AU - Li M AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Fang, Jinyu AU - Fang J AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Ding, Huiru AU - Ding H AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Meng, Jieyi AU - Meng J AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Zhang, Junwei AU - Zhang J AD - Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. FAU - Fang, Xuan AU - Fang X AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Liu, Huaicun AU - Liu H AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. FAU - Ma, Chao AU - Ma C AD - Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China. FAU - Chen, Chunhua AU - Chen C AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. Electronic address: cch@bjmu.edu.cn. FAU - Zhang, Weiguang AU - Zhang W AD - Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. Electronic address: zhangwg@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220812 PL - Netherlands TA - Redox Biol JT - Redox biology JID - 101605639 RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) SB - IM MH - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MH - Animals MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - In Situ Hybridization, Fluorescence MH - Mice MH - *MicroRNAs/genetics/metabolism MH - Oxidative Stress MH - *Parkinson Disease/genetics MH - RNA, Circular/genetics PMC - PMC9396399 OTO - NOTNLM OT - Akt1 OT - Foxk1 OT - Oxidative stress OT - circSV2b OT - miR-5107-5p COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/08/17 06:00 MHDA- 2022/09/28 06:00 PMCR- 2022/08/12 CRDT- 2022/08/16 18:24 PHST- 2022/06/20 00:00 [received] PHST- 2022/07/27 00:00 [revised] PHST- 2022/08/02 00:00 [accepted] PHST- 2022/08/17 06:00 [pubmed] PHST- 2022/09/28 06:00 [medline] PHST- 2022/08/16 18:24 [entrez] PHST- 2022/08/12 00:00 [pmc-release] AID - S2213-2317(22)00202-6 [pii] AID - 102430 [pii] AID - 10.1016/j.redox.2022.102430 [doi] PST - ppublish SO - Redox Biol. 2022 Oct;56:102430. doi: 10.1016/j.redox.2022.102430. Epub 2022 Aug 12.