期刊
WORLD NEUROSURGERY
卷 156, 期 -, 页码 E93-E103出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.wneu.2021.08.147
关键词
lncRNA; miR-519a-3p; NEAT1; PD; SP1
NEAT1 silencing protects against MPP+-induced neuroblastoma cell injury by regulating the miR-519a-3p/SP1 pathway, showing a potential therapeutic target for Parkinson's disease.
BACKGROUND: Parkinson disease is a neurodegenerative disease and is characterized by resting tremor, dementia, and gait disorder. Previous studies have indicated that long noncoding RNA participates in the regulation of the pathogenesis of Parkinson disease. The study aimed to reveal the effects of long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) on 1-methyl-4-phenylpyridine (MPP+)-induced human neuroblastoma cell injury and the underlying mechanism. METHODS: The expressions of NEAT1, microRNA (miR)-519a-3p, and transcription factor specific protein 1 (SP1) were detected by quantitative real-time polymerase chain reaction. The protein expressions of SP1 and inflammation-related factors were determined by Western blot. Cell viability was determined by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was investigated by flow cytometry analysis. The targeting relationship between miR-519a-3p and NEAT1 or SP1 was predicted by star-Base online database and verified by a dual-luciferase reporter assay. RESULTS: NEAT1 and SP1 expressions were significantly upregulated, whereas miR-519a-3p was down-regulated in MPP+-treated neuroblastoma cells in a dose- and time-dependent manner when compared with control groups. NEAT1 knockdown restrained MPP 'induced repression of cell viability and promotion of cell apoptosis apoptosis and inflammation. Additionally, NEAT1 served as a sponge of miR-519a-3p and regulated MPP+-caused cell injury by interacting with miR-519a-3p. Also, SP1, a target gene of miR-519a-3p, rescued miR-519a-3p-mediated actions under MPP+ treatment. Importantly, NEAT1 stimulated SP1 expression through interaction with miR-519a-3p. CONCLUSIONS: NEAT1 silencing protected against MPP+-induced neuroblastoma cell injury by regulating the miR-519a-3p/SP1 pathway. This finding provides a novel direction for the development of therapeutic strategies for Parkinson disease.
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