Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Long non-coding RNAs have important regulatory values in various human diseases. Non-coding RNA Activated by DNA Damage (NORAD) was reported to regulate PD progression in vitro, but its functional mechanism is fully unknown. We used 1-methyl-4-phenylpyridinium (MPP+ ) to establish the cell-based PD model. NORAD, microRNA-204-5p (miR-204-5p), and solute carrier family 5 member 3 (SLC5A3) levels were quantified using the quantitative real-time polymerase chain reaction. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry, respectively. The protein levels were analyzed via western blot. Cytotoxicity was assessed by the released lactate dehydrogenase level in cell supernatant. Oxidative stress and inflammation were measured by the standard indicators. Dual-luciferase reporter and RNA immunoprecipitation assays were performed for intergenic combination. First, we found that NORAD was obviously reduced in MPP+ -treated neuroblastoma cells and lightened the MPP+ -induced cytotoxicity, oxidative stress, and inflammatory response. Then, NORAD was shown to be a miR-204-5p sponge and avoided the injury induced by MPP+ in neuroblastoma cells via targeting miR-204-5p. SLC5A3 was a miR-204-5p target and could be regulated by NORAD/miR-204-5p axis. SLC5A3 knockdown assuaged the anti-miR-204-5p-induced protection for neuroblastoma cells from MPP+ . Altogether, NORAD played a neuroprotective role against the progression of MPP+ -induced PD model in neuroblastoma cells relying on the miR-204-5p/SLC5A3 axis. This study afforded the clear elaboration on the PD pathomechanism concerning NORAD.

中文翻译：

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长链非编码 RNA NORAD 作为 microRNA-204-5p 海绵发挥作用，通过增加溶质载体家族 5 成员 3 的表达来抑制体外帕金森病的进展

帕金森病 (PD) 是最常见的神经退行性疾病之一。长链非编码 RNA 在各种人类疾病中具有重要的调控价值。据报道，DNA 损伤激活的非编码 RNA (NORAD) 在体外调节 PD 进展，但其功能机制尚不清楚。我们使用 1-methyl-4-phenylpyridinium (MPP+) 来建立基于细胞的 PD 模型。NORAD、microRNA-204-5p (miR-204-5p) 和溶质载体家族 5 成员 3 (SLC5A3) 水平使用定量实时聚合酶链反应进行量化。细胞活力和细胞凋亡分别通过 Cell Counting Kit-8 和流式细胞术测定。通过蛋白质印迹分析蛋白质水平。通过细胞上清液中释放的乳酸脱氢酶水平来评估细胞毒性。氧化应激和炎症按标准指标测定。对基因间组合进行双荧光素酶报告基因和 RNA 免疫沉淀测定。首先，我们发现 MPP+ 处理的神经母细胞瘤细胞中 NORAD 明显减少，并减轻 MPP+ 诱导的细胞毒性、氧化应激和炎症反应。然后，NORAD 被证明是一种 miR-204-5p 海绵，并通过靶向 miR-204-5p 避免了 MPP+ 对神经母细胞瘤细胞的损伤。SLC5A3 是 miR-204-5p 靶标，可以受 NORAD/miR-204-5p 轴调节。SLC5A3 敲低减轻了抗 miR-204-5p 诱导的 MPP+ 对神经母细胞瘤细胞的保护。总之，NORAD 在神经母细胞瘤细胞中依赖 miR-204-5p/SLC5A3 轴对 MPP+ 诱导的 PD 模型的进展发挥了神经保护作用。