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LncRNA SNHG1 promotes neuronal injury in Parkinson’s disease cell model by miR-181a-5p/CXCL12 axis

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Abstract

Small molecule RNA host gene 1 (SNHG1) has been found to be an important regulator in the neurotoxicity of Parkinson’s disease (PD). However, the underlying molecular mechanisms of SNHG1 in PD remains elusive. The expression of SNHG1, microRNA (miR)-181a-5p, and C-X-C motif chemokine 12 (CXCL12) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability and apoptosis were analyzed by cell counting kit-8 and Flow cytometry, respectively. Western blot was utilized to determine the levels of B-cell lymphoma-2 (Bcl-2), CyclinD1, Cleaved-caspase-3, and CXCL12 protein. The interaction between miR-181a-5p and SNHG1 or CXCL12 was confirmed by the dual-luciferase reporter assay. We discovered that SNHG1 was significantly elevated, while miR-181a-5p was decreased in N-methyl-4-phenylpyridinium (MPP+)-treated neuroblastoma cells in dose-dependent manners. MPP+ induced cell viability inhibition and apoptosis promotion, while these effects were reversed by SNHG1 knockdown or miR-181a-5p re-expression. SNHG1 directly bound to miR-181a-5p, and miR-181a-5p inhibition could block the action of SNHG1 knockdown on MPP+-induced neurotoxicity in neuroblastoma cells. CXCL12 was identified as a downstream target of miR-181a-5p, and the impact of miR-181a-5p on MPP+-induced neuronal damage could be attenuated by CXCL12 overexpression. Besides, SNHG1 could indirectly regulate CXCL12 expression via miR-181a-5p. We demonstrated that SNHG1 promoted MPP+ induced neuronal injury in neuroblastoma cells by regulating miR-181a-5p/CXCL12 axis, suggesting SNHG1 might contribute to the development of PD, which provided a novel insight into the pathogenesis and treatment of PD.

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Authors and Affiliations

  1. Department of Internal Neurology, The 966th Hospital of the Joint Service Support Force, No.19, Shi**g Street, 118000, Dandong, Liaoning, China

    Hui Wang, **aopeng Wang & Jianchuan Zhao

  2. University of Army Engineering, Nan**g, Jiangsu, China

    Yiying Zhang

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  1. Hui Wang
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  2. **aopeng Wang
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  3. Yiying Zhang
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  4. Jianchuan Zhao
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Correspondence to Jianchuan Zhao.

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Wang, H., Wang, X., Zhang, Y. et al. LncRNA SNHG1 promotes neuronal injury in Parkinson’s disease cell model by miR-181a-5p/CXCL12 axis. J Mol Histol 52, 153–163 (2021). https://doi.org/10.1007/s10735-020-09931-3

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