Zhang Meng-Yi, Guo Bin-Han
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Transl Cancer Res. 2020 Jul;9(7):4306-4316. doi: 10.21037/tcr-19-2973.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Growing evidence supports a role for noncoding RNAs (ncRNAs) in CRC. In particular, they form competitive endogenous RNA (ceRNA) networks involved in the regulation of mRNA expression. However, the role of these networks in the pathogenesis of CRC is not fully understood. The aim of this study was to elucidate the role of circRNA/lncRNA-miRNA-mRNA systems in CRC pathogenesis based on the construction of a ceRNA network.
RNA expression profiles were obtained from public datasets in the Gene Expression Omnibus (GEO) database and used for further analysis by online databases and tools.
In total, 245 circRNAs, 1,666 lncRNAs, 5 miRNAs, and 934 mRNAs were differentially expressed in CRC samples. Functional enrichment analysis identified altered biological functions related to the mRNAs in the ceRNA network, and it was found that the oxytocin signaling pathway was significantly enriched (P<0.05) in genes with differential expression in CRC. Additionally, we established a protein-protein interaction (PPI) network and identified 10 hub genes for the construction of circRNA/lncRNA-miRNA-hub gene regulatory modules.
We identified several ncRNAs with a possible pathogenetic role in CRC and built a CRC-specific ceRNA network. The results of our study provide novel insights into the molecular events implicated in CRC.
结直肠癌(CRC)是全球癌症相关死亡的主要原因。越来越多的证据支持非编码RNA(ncRNAs)在CRC中发挥作用。特别是,它们形成了参与mRNA表达调控的竞争性内源RNA(ceRNA)网络。然而,这些网络在CRC发病机制中的作用尚未完全明确。本研究的目的是基于ceRNA网络的构建阐明circRNA/lncRNA-miRNA-mRNA系统在CRC发病机制中的作用。
从基因表达综合数据库(GEO)中的公共数据集中获取RNA表达谱,并通过在线数据库和工具进行进一步分析。
在CRC样本中,总共245种circRNA、1666种lncRNA、5种miRNA和934种mRNA存在差异表达。功能富集分析确定了ceRNA网络中与mRNA相关的生物学功能改变,并且发现在CRC中差异表达的基因中,催产素信号通路显著富集(P<0.05)。此外,我们建立了蛋白质-蛋白质相互作用(PPI)网络,并确定了10个枢纽基因用于构建circRNA/lncRNA-miRNA-枢纽基因调控模块。
我们鉴定了几种在CRC中可能具有致病作用的ncRNAs,并构建了一个CRC特异性的ceRNA网络。我们的研究结果为CRC相关的分子事件提供了新的见解。