Construction and characterization of rectal cancer-related lncRNA-mRNA ceRNA network reveals prognostic biomarkers in rectal cancer

IF 1.9 4区生物学 Q4 CELL BIOLOGY IET Systems Biology Pub Date : 2021-10-06 DOI:10.1049/syb2.12035

Guoying Cai, Meifei Sun, Xinrong Li, Junquan Zhu

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引用次数: 5

Abstract

Rectal cancer is an important cause of cancer-related deaths worldwide. In this study, the differentially expressed (DE) lncRNAs/mRNAs were first identified and the correlation level between DE lncRNAs and mRNAs were calculated. The results showed that genes of highly correlated lncRNA-mRNA pairs presented strong prognosis effects, such as GPM6A, METTL24, SCN7A, HAND2-AS1 and PDZRN4. Then, the rectal cancer-related lncRNA-mRNA network was constructed based on the ceRNA theory. Topological analysis of the network revealed that the network was maintained by hub nodes and a hub subnetwork was constructed, including the hub lncRNA MIR143HG and MBNL1-SA1. Further analysis indicated that the hub subnetwork was highly related to cancer pathways, such as ‘Focal adhesion’ and ‘Wnt signalling pathway’. Hub subnetwork also had significant prognosis capability. A closed lncRNA-mRNA module was identified by bilateral network clustering. Genes in modules also showed high prognosis effects. Finally, a core lncRNA-TF crosstalk network was identified to uncover the crosstalk and regulatory mechanisms of lncRNAs and TFs by integrating ceRNA crosstalks and TF binding affinities. Some core genes, such as MEIS1, GLI3 and HAND2-AS1 were considered as the key regulators in tumourigenesis. Based on the authors’ comprehensive analysis, all these lncRNA-mRNA crosstalks provided promising clues for biological prognosis of rectal cancer.

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直肠癌相关lncRNA-mRNA ceRNA网络的构建和表征揭示了直肠癌预后的生物标志物

直肠癌是全球癌症相关死亡的一个重要原因。本研究首先鉴定了差异表达(DE) lncRNAs/ mrna，并计算了DE lncRNAs与mrna之间的相关水平。结果显示，高度相关的lncRNA-mRNA对基因GPM6A、METTL24、SCN7A、HAND2-AS1和PDZRN4具有较强的预后作用。然后，基于ceRNA理论构建直肠癌相关lncRNA-mRNA网络。网络拓扑分析表明，该网络由枢纽节点维持，并构建了枢纽子网络，包括枢纽lncRNA MIR143HG和MBNL1-SA1。进一步分析表明，集线器子网络与癌症通路高度相关，如“局灶黏附”和“Wnt信号通路”。集线器子网也具有显著的预后能力。通过双边网络聚类鉴定出闭合的lncRNA-mRNA模块。模块中的基因也显示出较高的预后作用。最后，通过整合ceRNA串扰和TF的结合亲和力，确定了一个核心lncRNA-TF串扰网络，揭示了lncrna和TF的串扰和调控机制。一些核心基因如MEIS1、GLI3和HAND2-AS1被认为是肿瘤发生的关键调控因子。综合分析，这些lncRNA-mRNA串音为直肠癌生物学预后提供了有希望的线索。

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来源期刊

IET Systems Biology 生物-数学与计算生物学

CiteScore

4.20

自引率

4.30%

发文量

审稿时长

>12 weeks

期刊介绍： IET Systems Biology covers intra- and inter-cellular dynamics, using systems- and signal-oriented approaches. Papers that analyse genomic data in order to identify variables and basic relationships between them are considered if the results provide a basis for mathematical modelling and simulation of cellular dynamics. Manuscripts on molecular and cell biological studies are encouraged if the aim is a systems approach to dynamic interactions within and between cells. The scope includes the following topics: Genomics, transcriptomics, proteomics, metabolomics, cells, tissue and the physiome; molecular and cellular interaction, gene, cell and protein function; networks and pathways; metabolism and cell signalling; dynamics, regulation and control; systems, signals, and information; experimental data analysis; mathematical modelling, simulation and theoretical analysis; biological modelling, simulation, prediction and control; methodologies, databases, tools and algorithms for modelling and simulation; modelling, analysis and control of biological networks; synthetic biology and bioengineering based on systems biology.