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

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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.

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Data Availability

Original data generated in this study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Clinical Laboratory, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, Niaoning, China

    Cundi Zhong

  2. Rehabilitation Medicine, Sinopharm (Dalian) Rehabilitation Hospital, Dalian, 116013, Niaoning, China

    Qiang Zhang

  3. Neurology, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, 116023, Niaoning, China

    Haiping Bao, Yu Li & Chen Nie

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  1. Cundi Zhong
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by CN. Experiments were performed by QZ, HB, and YL. Data collection and analysis was performed by CZ. The first draft of the manuscript was written by CZ and CN. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Chen Nie.

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Zhong, C., Zhang, Q., Bao, H. et al. Hsa_circ_0054220 Upregulates HMGA1 by the Competitive RNA Pattern to Promote Neural Impairment in MPTP Model of Parkinson’s Disease. Appl Biochem Biotechnol (2023). https://doi.org/10.1007/s12010-023-04740-2

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