Differential Expression of MicroRNAs in Fibrotic Liver Tissues of Patients with Chronic Hepatitis B

Background: MicroRNAs (miRNAs), which are single-stranded small RNAs approximately 21 to 23 bases long, are involved in the regulation of cell proliferation, apoptosis, and lipid metabolism/fatty acid metabolism, and play important roles in the differentiation of the liver and the maintenance of its morphology and function MiRNAs are also closely related to the occurrence, development, treatment, and prognosis of liver diseases. Fibrotic Liver is a chronic process of the intrahepatic damage–repair response. The mixed effects of these pathogenic factors result in an abnormal comprehensive proliferation of fibrous tissue in the liver, diffused production and deposition of the extracellular matrix (ECM), and an imbalance in ECM synthesis and degradation. These lead to secondary inflammatory responses in the liver and the reversible pathological process of self-healing.Methods: Liver tissues were obtained from 3 patients with CHB with liver histopathological fibrosis grade ≥ S2, 2 patients with CHB with fibrosis grade < S2, and 1 healthy individual with a normal liver. The high-throughput miRNA microarray technique was used for miRNA expression analysis. The screening criteria for differential miRNA expression were a fold-change ≥ 2 and P< 0.005. The miRNAs with significantly different expression levels were verified by quantitative real-time PCR (qPCR), and the target gene functions were predicted by Gene Ontology (GO) and pathway analyses. Finally, an miRNA-gene network map was constructed.Results: In the CHB groups of tissues, 34 miRNAs with ≥ 2-fold difference in expression were found, of which 18 were upregulated and 16 were downregulated. qPCR was used to verify these miRNAs that showed significant differences, with the results showing consistency with the microarray results, indicating that the miRNA microarray results were credible. Bioinformatics analysis results demonstrate that some of the key upregulated miRNAs found in the network map were hsa-miR-125b-2-3p, hsa-miR-4639-3p, hsa-miR-4764-3p, and hsa-miR-3133, whereas some of the key downregulated ones were hsa-miR-1297, hsa-miR-154-5p, hsa-miR-3183 and hsa-miR-663a.Conclusion: In patients with CHB, the miRNA expression profile changes significantly with the severity of fibrotic liver. The development of fibrotic liver may be related to the miRNA-mediated regulation of cell development, metabolism, and apoptosis, and the positive/negative regulation of cell processes.This study was approved by the ethics committee of general hospital of Ningxia medical university (2015-134).