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一种基于通路交互分析挖掘肺腺癌特征 lncRNA 的新方法。

A new method for excavating feature lncRNA in lung adenocarcinoma based on pathway crosstalk analysis.

机构信息

Department of Electronic Engineering, College of Information Engineering, Shanghai Maritime University, Shanghai, China.

Department of Biochemistry, Rowan University and Guava Medicine, Glassboro, New Jersey.

出版信息

J Cell Biochem. 2019 Jun;120(6):9034-9046. doi: 10.1002/jcb.28177. Epub 2018 Dec 23.

Abstract

Recent theoretical and experimental studies indicate that long-chain noncoding RNAs (lncRNAs) are essential for the growth and differentiation of cells and the occurrence and development of tumors in epigenetics, but the regulation of lncRNA on gene expression, transcriptional activation, and transcriptional interference in diseases is still unclear. There is an urgent need for effective methods to discover significant lncRNAs with their functions on gene regulatory mechanisms. For this purpose, a new method of extracting significant lncRNA based on pathway crosstalk and dysfunction caused by the differentially expressed genes in lung adenocarcinoma (LUAD) was proposed. The pathway analysis method based on global influence (PAGI) was first applied to find the feature genes that play an important role in the crosstalks of disease-related pathways. Then to explore the hub lncRNAs, the weighted gene coexpression network analysis (WGCNA) was used to construct coexpression models of the feature genes and lncRNAs. The experiment results showed that 64 out of the 322 hub lncRNAs were closely related to the clinical features of patients with LUAD. Among them, nine lncRNAs (UCA1, LINC00857, PVT1, PCAT6, LINC00460, LINC00319, AP000553.1, AP000439.2, and AP005233.2) were identified to be tightly correlated with non-small-cell lung cancer (NSCLC) pathways. In summary, we offer an effective way to extract significant lncRNA by dysfunctional pathway crosstalk in LUAD which allows the selected lncRNAs with more biologically interpreted and reproducible results. This method can be applied to other diseases and provide useful information for understanding the pathogenesis of human cancer.

摘要

最近的理论和实验研究表明,长链非编码 RNA(lncRNA)在表观遗传学中对细胞的生长和分化以及肿瘤的发生和发展至关重要,但其在疾病中对基因表达、转录激活和转录干扰的调控仍不清楚。迫切需要有效的方法来发现具有基因调控机制功能的显著 lncRNA。为此,提出了一种基于肺腺癌(LUAD)差异表达基因引起的通路串扰和功能障碍来提取显著 lncRNA 的新方法。首先应用基于全局影响的通路分析方法(PAGI)来寻找在疾病相关通路串扰中起重要作用的特征基因。然后,为了探索枢纽 lncRNA,使用加权基因共表达网络分析(WGCNA)构建特征基因和 lncRNA 的共表达模型。实验结果表明,322 个枢纽 lncRNA 中有 64 个与 LUAD 患者的临床特征密切相关。其中,9 个 lncRNA(UCA1、LINC00857、PVT1、PCAT6、LINC00460、LINC00319、AP000553.1、AP000439.2 和 AP005233.2)被确定与非小细胞肺癌(NSCLC)通路紧密相关。总之,我们提供了一种通过 LUAD 中功能障碍的通路串扰提取显著 lncRNA 的有效方法,从而选择具有更多生物学解释和可重复结果的 lncRNA。该方法可应用于其他疾病,并为理解人类癌症的发病机制提供有用信息。

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