Hsa_circ_0054220 Upregulates HMGA1 by the Competitive RNA Pattern to Promote Neural Impairment in MPTP Model of Parkinson’s Disease

• Published in: Applied biochemistry and biotechnology 2024-07, Vol.196 (7), p.4008-4023
• Main Authors: Zhong, Cundi, Zhang, Qiang, Bao, Haiping, Li, Yu, Nie, Chen
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis; Assaying; Biochemistry; Biotechnology; Cell Line, Tumor; Cell viability; Chemistry; Chemistry and Materials Science; Cholecystokinin; Circular RNA; Disease; Disease Models, Animal; Gene expression; HMGA1a Protein - genetics; HMGA1a Protein - metabolism; Humans; Impairment; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Movement disorders; MPTP; MPTP Poisoning - genetics; MPTP Poisoning - metabolism; Neostriatum; Neurodegenerative diseases; Original Article; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Ribonucleic acid; RNA; RNA, Circular - genetics; RNA, Circular - metabolism; Substantia nigra; Up-Regulation
• ISSN: 0273-2289; 1559-0291; 1559-0291
• DOI: 10.1007/s12010-023-04740-2

Parkinson’s disease (PD) is a common neurodegenerative disease. Circular RNAs (circRNAs) have been confirmed to regulate neurodegenerative diseases. This study was aimed to explore hsa_circ_0054220 functions in PD. MPP-stimulated SH-SY5Y cells were established as the PD cell model. PD mouse model was established by MPTP. Gene expression in cells and tissues was tested by RT-qPCR. Cell viability and apoptosis were evaluated through CCK-8 and TUNEL assays. The interactions of RNAs were determined by RNA pull-down assay, RIP assay, and luciferase reporter assay. Circ_0054220 expressed at a high level in MPP-treated SH-SY5Y cells. Circ_0054220 inhibition promoted viability and suppressed apoptosis in MPP-stimulated cells. Furthermore, we found that circ_0054220 can competitively bind to miR-145 and miR-625 to upregulate high mobility group A1 (HMGA1) expression. HMGA1 was positively regulated by circ_0054220 and overexpressed in MPP-treated cells as well as the striatum (STR), substantia nigra pars compacta (SNpc), and serum of MPTP-induced mouse model of PD. HMGA1 overexpression counteracted the function of circ_0054220 silencing on cell apoptosis. Furthermore, HMGA1 inhibition notably alleviated motor dysfunction and increased the quantity of neurons in mice resembling PD. Circ_0054220 upregulates HMGA1 by the competitive endogenous RNAs (ceRNA) pattern to promote neural impairment in PD. Graphical Abstract