人亨廷顿神经前体细胞差异表达基因的综合分析及竞争性内源 RNA 网络的构建。
Integrated analysis of differentially expressed genes and construction of a competing endogenous RNA network in human Huntington neural progenitor cells.
机构信息
Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China.
出版信息
BMC Med Genomics. 2021 Feb 12;14(1):48. doi: 10.1186/s12920-021-00894-2.
BACKGROUND
Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking.
METHODS
In this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs.
RESULTS
We identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors.
CONCLUSIONS
Our research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.
背景
亨廷顿病（HD）是最常见的多聚谷氨酰胺疾病之一，导致进行性运动障碍、认知障碍和神经心理问题。除了 HD 中许多蛋白质编码基因的失调外，先前的研究还揭示了多种非编码 RNA 也在 HD 中失调，包括几种长非编码 RNA（lncRNA）。然而，基于竞争内源性 RNA（ceRNA）网络的差异表达（DE）基因的综合分析目前仍然缺乏。
方法
在这项研究中，我们系统地分析了来自 HD 患者和对照（健康对照和使用 CRISPR-Cas9 方法在 HTT 基因座校正的 HD 患者细胞系的同基因对照）的神经祖细胞（NPC）的基因表达谱数据，以筛选出 DE mRNAs 和 DE lncRNAs，并创建 ceRNA 网络。为了更深入地了解 lncRNA 在 HD 中 ceRNA 调控网络中的可能功能，我们对 GO 和 KEGG 进行了功能分析，并建立了与这些 lncRNA 相互作用的 mRNAs 的蛋白质-蛋白质相互作用（PPI）网络。
结果
我们分别鉴定出 490 个 DE mRNAs 和 94 个 DE lncRNAs，其中 189 个 mRNAs 和 20 个 lncRNAs 被应用于创建 ceRNA 网络。结果表明，DE lncRNAs 的功能主要与转录调控相关，GO 分析表明。此外，KEGG 富集分析表明这些 lncRNAs 参与了肿瘤坏死因子、钙、Wnt 和 NF-kappa B 信号通路。有趣的是，PPI 网络表明 ceRNA 网络中的多种转录因子相互作用，表明这些 lncRNA 可能通过控制这些蛋白质编码基因的表达来调节 HD 中的转录，特别是转录因子。
结论
我们的研究为揭示 lncRNA 在 HD 中的作用机制提供了新的线索，并可作为进一步研究的重点。
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