Niemann-Pick type C (NP-C) disease is a neurodegenerative lysosomal storage disorder primarily caused by mutations in NPC1. However, its pathogenesis remains poorly understood. While mounting evidence has demonstrated the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of neurodegenerative disorders, the lncRNA expression profile in NP-C has not been determined. Here, we used RNA-seq analysis to determine lncRNA and mRNA expression profiles of the cerebella of NPC1^−/− mice. We found that 272 lncRNAs and 856 mRNAs were significantly dysregulated in NPC1^−/− mice relative to controls (≥ 2.0-fold, p < 0.05). Quantitative real-time PCR (qRT‐PCR) was utilized to validate the expression of selected lncRNAs and mRNAs. Next, a lncRNA-mRNA coexpression network was employed to examine the potential roles of the differentially expressed (DE) lncRNAs. Functional analysis revealed that mRNAs coexpressed with lncRNAs are mainly linked to immune system–related processes and neuroinflammation. Moreover, knockdown of the lncRNA H19 ameliorated changes in ROS levels and cell viability and suppressed the lipopolysaccharide (LPS)–induced inflammatory response in vitro. Our findings indicate that dysregulated lncRNA expression patterns are associated with NP-C pathogenesis and offer insight into the development of novel therapeutics based on lncRNAs.

Niemann-Pick C 型 (NP-C) 病是一种神经退行性溶酶体贮积症，主要由NPC1突变引起。然而，其发病机制仍知之甚少。虽然越来越多的证据表明长链非编码 RNA (lncRNA) 参与了神经退行性疾病的发病机制，但 NP-C 中的 lncRNA 表达谱尚未确定。在这里，我们使用 RNA-seq 分析来确定 NPC1 ^-/-小鼠小脑的 lncRNA 和 mRNA 表达谱。我们发现 NPC1 ^-/-小鼠相对于对照组有 272 个 lncRNA 和 856 个 mRNA 显着失调（≥ 2.0 倍，p < 0.05)。定量实时 PCR (qRT-PCR) 用于验证选定的 lncRNA 和 mRNA 的表达。接下来，使用 lncRNA-mRNA 共表达网络来检查差异表达 (DE) lncRNA 的潜在作用。功能分析表明，与 lncRNA 共表达的 mRNA 主要与免疫系统相关过程和神经炎症有关。此外，敲除 lncRNA H19 可改善 ROS 水平和细胞活力的变化，并抑制脂多糖 (LPS) 诱导的体外炎症反应。我们的研究结果表明，失调的 lncRNA 表达模式与 NP-C 发病机制相关，并为基于 lncRNA 的新疗法的开发提供了见解。