基于高通量测序的肝癌circRNA-miRNA-mRNA调控网络构建及功能富集分析

Abstract

摘要:

目的本研究基于肝癌相关非编码RNA高通量测序数据,构建互作网络及功能富集分析,筛选可能通过竞争性内源RNA (ceRNA) 机制参与肝癌发生发展的环状RNA (circRNA) 。方法利用GEO数据库中的肝癌非编码RNA高通量测序数据,依据ceRNA理论构建circRNA-miRNA-mRNA网络。随后,进行了基因本体论分析 (GO) 和京都基因与基因组百科全书 (KEGG) 分析,用于具有ceRNA潜在功能的circRNA的探索及功能注释。结果从GEO数据库中最终筛选了9个共表达circRNAs、20个共表达miRNAs以及153个共表达mRNAs,成功构建肝癌相关circRNA-miRNA-mRNA网络。GO分析结果揭示了90个生物过程,其主要涉及12个功能簇,主要包括肝细胞分化、细胞周期相变调节、转录因子活性负调控等功能,KEGG分析表明这些共表达circRNAs还参与p53、PI3K-Akt信号通路。结论本研究为circRNA通过ceRNA机制介导肝癌发生发展提供了新的见解。

Alternate abstract:

Objective To construct a protein interaction network based on high-throughput sequencing data of liver cancer-related non-coding RNAs, to perform a functional enrichment analysis, and to screen out circular RNAs (circRNAs) participating in the development and progression of liver cancer via the mechanism of competitive endogenous RNA (ceRNA) . Methods The circRNA-miRNA-mRNA network was constructed using gene expression omnibus (GEO) data based on the ceRNA theory. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses were performed to identify circRNAs with potential ceRNA function and explore their functions. Results A total of 9 co-expressed circRNAs, 20 co-expressed miRNAs, and 153 co-expressed mRNAs were screened out from the GEO database, and the liver cancer-related circRNA-miRNA-mRNA network was successfully constructed. The GO analysis revealed 90 biological processes, which mainly involved 12 functional clusters including hepatocyte differentiation, phase-change regulation of cell cycle, and negative regulation of transcription factor activity. The KEGG analysis showed that the co-expressed circRNAs were also involved in the p53 and PI3 K-Akt signaling pathways. Conclusion This study provides new insights for circRNAs mediating the development and progression of liver cancer through the mechanism of ceRNA.