This study was to identify important circRNA-miRNA-mRNA (ceRNAs) regulatory mechanisms in hepatocellular carcinoma (HCC). The circRNA dataset GSE97332 and miRNA dataset GSE57555 were used for analyses. Functional enrichment analysis for miRNA and target gene was conducted using cluster Profiler. Survival analysis was conducted through R package Survival. The ceRNAs and drug-gene interaction networks were constructed. The ceRNAs network contained five miRNAs including hsa-miR-25-3p, hsa-miR-3692-5p, hsa-miR-4270, hsa-miR-331-3p, and hsa-miR-125a-3p. Among the network, hsa-miR-25-3p targeted the most genes, hsa-miR-3692-5p and hsa-miR-4270 were targeted by more circRNAs than other miRNAs, hsa-circ-0034326 and hsa-circ-0011950 interacted with three miRNAs. Furthermore, target genes, including NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were obtained in drug-gene interaction network. Survival analysis showed NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were significantly associated with prognosis of HCC. NRAS, ITGA5, and SMAD2 were significantly enriched in proteoglycans in cancer. Moreover, hsa-circ-0034326 and hsa-circ-0011950 might function as ceRNAs to play key roles in HCC. Furthermore, miR-25-3p, miR-3692-5p, and miR-4270 might be significant for HCC development. NRAS, ITGA5, SEC14L2, SLC12A5, and SMAD2 might be prognostic factors for HCC patients via proteoglycans in cancer pathway. Taken together, the findings will provide novel insight into pathogenesis, selection of therapeutic targets and prognostic factors for HCC.

中文翻译：

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肝细胞癌中circRNA-miRNA-mRNA调控网络的鉴定与分析。


本研究旨在确定肝细胞癌 (HCC) 中重要的 circRNA-miRNA-mRNA (ceRNA) 调节机制。使用circRNA数据集GSE97332和miRNA数据集GSE57555进行分析。使用Cluster Profiler对miRNA和靶基因进行功能富集分析。通过R包Survival进行生存分析。构建了 ceRNA 和药物-基因相互作用网络。 ceRNA 网络包含 5 个 miRNA，包括 hsa-miR-25-3p、hsa-miR-3692-5p、hsa-miR-4270、hsa-miR-331-3p 和 hsa-miR-125a-3p。在网络中，hsa-miR-25-3p靶向最多的基因，hsa-miR-3692-5p和hsa-miR-4270比其他miRNA被更多的circRNA靶向，hsa-circ-0034326和hsa-circ-0011950相互作用具有三个 miRNA。此外，在药物-基因相互作用网络中获得了靶基因，包括NRAS、ITGA5、SLC7A1、SEC14L2、SLC12A5和SMAD2。生存分析显示NRAS、ITGA5、SLC7A1、SEC14L2、SLC12A5和SMAD2与HCC预后显着相关。 NRAS、ITGA5 和 SMAD2 在癌症中的蛋白聚糖显着富集。此外，hsa-circ-0034326和hsa-circ-0011950可能作为ceRNA在HCC中发挥关键作用。此外，miR-25-3p、miR-3692-5p 和 miR-4270 可能对 HCC 的发展具有重要意义。 NRAS、ITGA5、SEC14L2、SLC12A5 和 SMAD2 可能通过癌症通路中的蛋白多糖成为 HCC 患者的预后因素。总而言之，这些发现将为 HCC 的发病机制、治疗靶点的选择和预后因素提供新的见解。