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

IF 3.1 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Applied Biochemistry and Biotechnology Pub Date : 2023-10-10 DOI:10.1007/s12010-023-04740-2

Cundi Zhong, Qiang Zhang, Haiping Bao, Yu Li, Chen Nie

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Abstract

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

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Hsa_cir_0054220通过竞争性RNA模式上调HMGA1以促进帕金森病MPTP模型中的神经损伤。

帕金森病是一种常见的神经退行性疾病。环状核糖核酸（circRNAs）已被证实可调节神经退行性疾病。本研究旨在探讨hsa_cir_0054220在PD中的作用。建立了MPP刺激的SH-SY5Y细胞作为PD细胞模型。MPTP法建立PD小鼠模型。通过RT-qPCR检测细胞和组织中的基因表达。通过CCK-8和TUNEL测定评估细胞活力和凋亡。通过RNA下拉测定法、RIP测定法和荧光素酶报告基因测定法测定RNA的相互作用。Circ_ 0054220在MPP处理的SH-SY5Y细胞中高水平表达。Circ_0054220抑制促进了MPP刺激的细胞的生存能力并抑制了细胞凋亡。此外，我们发现circ_0054220可以与miR-145和miR-625竞争性结合，上调高迁移率A1组（HMGA1）的表达。HMGA1受circ_0054220的正调控，并在MPP处理的细胞以及MPTP诱导的PD小鼠模型的纹状体（STR）、黑质致密部（SNpc）和血清中过表达。HMGA1过表达抵消了circ_0054120沉默对细胞凋亡的作用。此外，HMGA1的抑制显著减轻了类似PD的小鼠的运动功能障碍，并增加了神经元的数量。Circ_0054220通过竞争性内源性RNA（ceRNA）模式上调HMGA1，以促进PD的神经损伤。

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来源期刊

Applied Biochemistry and Biotechnology 工程技术-生化与分子生物学

CiteScore

5.70

自引率

6.70%

发文量

460

审稿时长

5.3 months

期刊介绍： This journal is devoted to publishing the highest quality innovative papers in the fields of biochemistry and biotechnology. The typical focus of the journal is to report applications of novel scientific and technological breakthroughs, as well as technological subjects that are still in the proof-of-concept stage. Applied Biochemistry and Biotechnology provides a forum for case studies and practical concepts of biotechnology, utilization, including controls, statistical data analysis, problem descriptions unique to a particular application, and bioprocess economic analyses. The journal publishes reviews deemed of interest to readers, as well as book reviews, meeting and symposia notices, and news items relating to biotechnology in both the industrial and academic communities. In addition, Applied Biochemistry and Biotechnology often publishes lists of patents and publications of special interest to readers.