Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
J Cell Mol Med. 2021 Sep;25(18):9066-9071. doi: 10.1111/jcmm.16838. Epub 2021 Aug 8.
Emerging studies have suggested that dysregulated long non-coding RNAs (lncRNAs) are associated with the pathogenesis of neurodegenerative diseases (NDD) including Huntington's disease (HD); however, the pathophysiological mechanism by which lncRNA dysregulation participates in HD remains to be elucidated. Here, we aim to analyse the expression of lncRNA-DNM3OS and identify the possible DNM3OS/miR-196b-5p/GAPDH pathway. PC12 cells induced by rat pheochromocytoma expressing HD gene exon 1 fragment with either 23 or 74 polyglutamine repeats fused to the green fluorescent protein (GFP) were cultured. Our results show that GAPDH and DNM3OS were upregulated in HD PC12 cells, downregulation of which lead to inhibition of aggregate formation accompanied by a decreased apoptosis rate and increased relative ROS levels and cell viability. Moreover, upregulated DNM3OS decreased the expression of miR-196b-5p by sponging, and GAPDH was a direct target of miR-196b-5p, playing an important pathogenic role in the formation of aggregates in the HD cell model. Our study uncovers a novel DNM3OS/miR-196b-5p/GAPDH pathway involved in the molecular pathogenesis of HD, which may offer a potential therapeutic strategy for HD.
新兴研究表明，失调的长非编码 RNA（lncRNA）与神经退行性疾病（NDD）的发病机制有关，包括亨廷顿病（HD）；然而，lncRNA 失调参与 HD 的病理生理机制仍有待阐明。在这里，我们旨在分析 lncRNA-DNM3OS 的表达，并确定可能的 DNM3OS/miR-196b-5p/GAPDH 通路。培养表达 HD 基因外显子 1 片段的大鼠嗜铬细胞瘤的 PC12 细胞，该片段融合了绿色荧光蛋白（GFP），其具有 23 或 74 个多聚谷氨酰胺重复序列。我们的结果表明，HD PC12 细胞中 GAPDH 和 DNM3OS 上调，下调后可抑制聚集物形成，同时降低细胞凋亡率，增加相对 ROS 水平和细胞活力。此外，上调的 DNM3OS 通过海绵作用降低了 miR-196b-5p 的表达，而 GAPDH 是 miR-196b-5p 的直接靶标，在 HD 细胞模型中对聚集物的形成起着重要的致病作用。我们的研究揭示了一个新的 DNM3OS/miR-196b-5p/GAPDH 通路，参与了 HD 的分子发病机制，这可能为 HD 提供了一种潜在的治疗策略。
