Discovering new biomarkers of primary liver cancer by establishing an mRNA-miRNA-lncRNA network

In recent years, the competitive endogenous RNA (ceRNA) concept has become a key mechanism for understanding gene expression regulation. Although there has been extensive research into ceRNA networks within the context of liver cancer, the differentiation between disease stages is still not well-defined. This study aims to establish a ceRNA network that includes mRNA, MiRNA, and lncRNA interactions specific to stage I liver cancer in comparison to normal liver tissues. Firstly, significant changes of RNAs expression have been identified: 1,167 mRNAs were upregulated, and 3,224 were downregulated. Additionally, we observed 4 upregulated and 36 downregulated miRNAs. In terms of lncRNAs, 618 were upregulated and 2,350 were downregulated. Secondly, two lncRNA-miRNA-mRNA networks have been successfully established based on the ceRNA hypothesis. One network is centered around hsa-miR-4686, which is connected to 70 downregulated mRNAs and the downregulated lncRNA GAS5. The other network involves the downregulated miRNAs hsa-miR-765 and hsa-miR-3176, linked to 84 upregulated mRNAs and two upregulated lncRNAs, AP000439.2 and LINC00598. This finding is the first to reveal the influence of hsa-miR-4686 and hsa-miR-3176 in liver cancer. Through survival analysis, we identified SERPINE1, SIRPB1, SMIM14, TRPM8, and ZNF878 as genes associated with poor prognosis. Additionally, our study suggests that the interaction between GAS5 and hsa-miR-4686 may represent a novel regulatory mechanism. These findings could provide new biomarkers for early-stage hepatocellular carcinoma (HCC).