Donyavi Mohammad Hossein, Salehi-Mazandarani Sadra, Nikpour Parvaneh
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Iran J Basic Med Sci. 2022 Mar;25(3):286-294. doi: 10.22038/IJBMS.2022.61570.13623.
Hepatocellular carcinoma (HCC) is a common and lethal type of cancer worldwide. The importance of non-coding RNAs such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been recognized in the development of HCC. In this study, we constructed a four-component competing endogenous RNA (ceRNA) network in HCC and evaluated prognostic values of the ceRNAs.
The expression profiles of lncRNAs, miRNAs, and mRNAs were retrieved from The Cancer Genome Atlas database. GSE94508 and GSE97332 studies from the Gene Expression Omnibus database were used to identify circRNAs expression profiles. A four-component ceRNA network was constructed based on differentially-expressed RNAs. Survival R package was utilized to identify potential prognostic biomarkers.
A four-component ceRNA network including 295 edges and 239 nodes was constructed and enrichment analysis revealed important Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A Protein-Protein Interaction network with 118 nodes and 301 edges was also established. The enhancer of zeste homolog 2 (EZH2) was the highest degree hub gene in the PPI network. Because of the significance of EZH2 in HCC, we presented its axes in the ceRNA network, which play important roles in HCC progression. Furthermore, ceRNAs were identified as potential prognostic biomarkers utilizing survival analysis.
Our study elucidates the role of ceRNAs and their regulatory interactions in the pathogenesis of HCC and identifies EZH2-related RNAs which may be utilized as novel therapeutic targets and prognostic biomarkers in the future.
肝细胞癌(HCC)是全球常见且致命的癌症类型。长链非编码RNA(lncRNA)、环状RNA(circRNA)和微小RNA(miRNA)等非编码RNA在HCC发生发展中的重要性已得到认可。在本研究中,我们构建了HCC中的四组分竞争性内源RNA(ceRNA)网络,并评估了ceRNA的预后价值。
从癌症基因组图谱数据库中检索lncRNA、miRNA和mRNA的表达谱。使用基因表达综合数据库中的GSE94508和GSE97332研究来鉴定circRNA表达谱。基于差异表达的RNA构建了四组分ceRNA网络。利用生存R包来鉴定潜在的预后生物标志物。
构建了一个包含295条边和239个节点的四组分ceRNA网络,富集分析揭示了重要的基因本体论和京都基因与基因组百科全书途径。还建立了一个具有118个节点和301条边的蛋白质-蛋白质相互作用网络。zeste同源物2增强子(EZH2)是PPI网络中连接度最高的中心基因。由于EZH2在HCC中的重要性,我们展示了其在ceRNA网络中的轴,它们在HCC进展中起重要作用。此外,利用生存分析将ceRNA鉴定为潜在的预后生物标志物。
我们的研究阐明了ceRNA及其调控相互作用在HCC发病机制中的作用,并鉴定了与EZH2相关的RNA,它们未来可能用作新的治疗靶点和预后生物标志物。