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.

中文翻译：

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DNM3OS 调节 GAPDH 表达并影响亨廷顿病的分子发病机制

新兴研究表明，失调的长链非编码 RNA (lncRNA) 与包括亨廷顿病 (HD) 在内的神经退行性疾病 (NDD) 的发病机制有关。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。培养由表达 HD 基因外显子 1 片段的大鼠嗜铬细胞瘤诱导的 PC12 细胞，其中 23 或 74 个聚谷氨酰胺重复与绿色荧光蛋白 (GFP) 融合。我们的研究结果表明，GAPDH 和 DNM3OS 在 HD PC12 细胞中上调，其下调导致聚集物形成受到抑制，伴随着细胞凋亡率降低和相对 ROS 水平和细胞活力增加。而且，上调的 DNM3OS 通过海绵作用降低 miR-196b-5p 的表达，GAPDH 是 miR-196b-5p 的直接靶标，在 HD 细胞模型中聚集体的形成中起重要的致病作用。我们的研究揭示了一种新的 DNM3OS/miR-196b-5p/GAPDH 通路参与 HD 的分子发病机制，这可能为 HD 提供潜在的治疗策略。