长链非编码 RNA-UCA1 通过上调 SNCA 促进 PD 的发展。
LncRNA-UCA1 promotes PD development by upregulating SNCA.
机构信息
Department of Rehabilitation Medicine, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Nov;22(22):7908-7915. doi: 10.26355/eurrev_201811_16417.
OBJECTIVE
The study aims to investigate whether Long non-coding RNA (LncRNA)-UCA1 can regulate the progression of Parkinson's disease (PD) by mediating a-synuclein (SNCA) expression.
MATERIALS AND METHODS
PD mouse model was first constructed by intraperitoneal injection of MPTP. SH-SY5Y cells were treated with MPP+ for inducing in vitro PD model. Expression levels of lncRNA-UCA1 and SNCA in brain tissues extracted from PD mice and MPP+-induced SH-SY5Y cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression of SNCA was accessed by Western blot. After transfection of pcDNA-NC+DMSO, pcDNA-UCA1+DMSO, pcDNA-NC+α-amantin or pcDNA-UCA1+α-amanitin in SH-SY5Y cells, SNCA expression was detected. Cell viability and SNCA expression were determined after UCA1 overexpression or knockdown in SH-SY5Y cells. Neuronal apoptosis in MPP+-induced SH-SY5Y cells was detected by flow cytometry after the UCA1 knockdown.
RESULTS
UCA1 and SNCA were highly expressed in brain tissues extracted from PD mice and MPP+-induced SH-SY5Y cells. UCA1 overexpression remarkably upregulated mRNA and protein expressions of SNCA in SH-SY5Y cells. Higher viability was seen after the UCA1 knockdown in MPP+-induced SH-SY5Y cells. UCA1 knockdown remarkably inhibited caspase-3 activity and decreased MPP+-induced neuronal apoptosis in SH-SY5Y cells.
CONCLUSIONS
LncRNA-UCA1 promotes the occurrence and progression of PD by upregulating SNCA expression.
目的
本研究旨在探讨长链非编码 RNA（LncRNA）-UCA1 是否可以通过调节α-突触核蛋白（SNCA）的表达来调节帕金森病（PD）的进展。
材料与方法
首先通过腹腔注射 MPTP 构建 PD 小鼠模型。用 MPP+处理 SH-SY5Y 细胞以诱导体外 PD 模型。通过实时定量聚合酶链反应（qRT-PCR）检测从 PD 小鼠和 MPP+-诱导的 SH-SY5Y 细胞中提取的脑组织中的 lncRNA-UCA1 和 SNCA 的表达水平。通过 Western blot 检测 SNCA 的蛋白表达。在 SH-SY5Y 细胞中转染 pcDNA-NC+DMSO、pcDNA-UCA1+DMSO、pcDNA-NC+α-amanitin 或 pcDNA-UCA1+α-amanitin 后，检测 SNCA 的表达。在 SH-SY5Y 细胞中转染 UCA1 过表达或敲低后，检测细胞活力和 SNCA 的表达。用流式细胞术检测 MPP+-诱导的 SH-SY5Y 细胞中 UCA1 敲低后神经元凋亡情况。
结果
UCA1 和 SNCA 在从 PD 小鼠和 MPP+-诱导的 SH-SY5Y 细胞中提取的脑组织中高表达。UCA1 过表达显著上调 SH-SY5Y 细胞中 SNCA 的 mRNA 和蛋白表达。在 MPP+-诱导的 SH-SY5Y 细胞中 UCA1 敲低后，细胞活力更高。UCA1 敲低显著抑制 caspase-3 活性并减少 MPP+-诱导的 SH-SY5Y 细胞中的神经元凋亡。
结论
LncRNA-UCA1 通过上调 SNCA 的表达促进 PD 的发生和发展。
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