Hsa_Circ_0105596/FTO inhibits progression of Parkinson's disease by sponging miR-187-3p and regulating eEF2

• DOI: 10.1016/j.heliyon.2024.e39830
• Publication Date: 2024-11-02T23:32:31Z
• Authors: Jiahao Feng; Jin Zhao; Yong Kuang; Yuheng Zhou; Ziheng Ye; Yutong He; Dandan Chen; Li Zhang; Tingying Zhang; Qingqing Zhu; Shumin Cheng; Taoli Liu
• Keywords: Social sciences (General); H1-99; 0301 basic medicine; Q1-390; 03 medical and health sciences; Parkinson's disease (PD); Science (General); Neuronal apoptosis; Hsa_Circ_0105596 (circFTO); Transcriptome analysis; miR-187-3p; Research Article

Parkinson's disease (PD) characterized by inflammation and protein erroneous deposition, whose pathological mechanisms have not been elucidated. NcRNA plays important role in PD, especially when circRNA sponges miRNA, which leads to the breakdown of downstream regulation. The aim this study is investigate dynamic changes between upregulated downregulated miRNA during pathogenesis PD their impact on targets. We conducted bioinformatics sequencing data substantia nigra (SN) striatum, intersected differentially expressed genes (Degs) determine core circFTO-miR-187-3p-EEF2 axes progression PD. Firstly, therapeutic effect knock-down circFTO its EEF2 were determined mouse, using immunohistochemistry, HE, Nissl, TUNEL staining Western blot (WB). Targeted binding relationship circFTO, miR-187-3p, was through RNA immunoprecipitation assays (RIP) dual luciferase reporter assay. significance gene apoptosis confirmed flow cytometry, lentiviral transduction, quantitative real-time PCR, WB. CircFTO miR-187-3p SN neural repair related modules both striatum Weighted Correlation Network Analysis (WGCNA) protein-protein interaction (PPI). regulation structural analysis, RIP, After knocking-down animals showed alleviated symptoms, decreased levels oxidative stress EEF2. Upregulation or si-circFTO SH-SY5Y cells can reduce cell apoptosis, EEF2, stress. Moreover, individual interference with partially counteract induction 6-OHDA apoptosis. Excessive sponging inability effectively regulate expression resulting brain