Construction and Bioinformatics Analysis of the miRNA-mRNA Regulatory Network in Liver regeneration in rats

Background: Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors. Partial hepatectomy (PHx) is currently the primary treatment for HCC, but many patients suffer from poor liver reserve function and insufficient remaining liver volume, limiting the liver's regenerative capacity. Therefore, this study aims to explore the mechanisms of miRNA and mRNA in liver regeneration through high-throughput sequencing. Methods: A rat model of 70% hepatectomy was used, and physiological indicators related to liver regeneration were assessed on days 3, 7, and 14 post-surgery. Small RNA sequencing and transcriptome analysis were conducted to evaluate the miRNA and mRNA expression profiles at different stages of regeneration. Bioinformatics tools were used to identify differentially expressed genes, construct miRNA-mRNA regulatory networks, and protein-protein interaction (PPI) networks, to identify key regulatory molecules. Results: The rat liver regeneration model was successfully established, and the body weight and liver regeneration rate data on days 3, 7, and 14 indicated a smooth regeneration process. Small RNA sequencing and transcriptome analysis identified 395 known miRNAs and 299 precursor miRNAs. Differential expression analysis revealed dynamic expression patterns of multiple miRNAs and mRNAs during liver regeneration. The miRNA-mRNA regulatory network showed interactions between 17 differentially expressed miRNAs and 31 differentially expressed mRNAs involved in liver regeneration. Conclusion: This study, through small RNA sequencing and transcriptome analysis, revealed key regulatory roles of miRNAs in various signaling pathways during liver regeneration. The constructed miRNA-mRNA regulatory network further elucidates the molecular mechanisms of liver regeneration. The results demonstrate the complex regulatory roles of miRNAs in promoting hepatocyte proliferation, inhibiting apoptosis, and regulating multiple key signaling pathways, providing new insights into the understanding of liver regeneration mechanisms.