Identification of Potential miRNA-mRNA Regulatory Axis of Intrahepatic cccDNA in Patients with Chronic Hepatitis B Virus Infection in the Grey Zone

Background: Intrahepatic covalently closed circular DNA (cccDNA) plays a critical role in the life cycle of hepatitis B virus (HBV). Growing evidence suggests that microRNAs (miRNAs) may regulate cccDNA expression and contribute to natural history chronic (CHB). Objectives: This study aimed investigate potential miRNA-mRNA regulatory axes intrahepatic CHB-GZ patients identify new therapeutic targets. Methods: Thirteen were included divided into two groups based on levels: Reference group (n = 7) with < 1 copy/cell control 6) ≥ copy/cell. Transcriptome-wide miRNA mRNA profiles liver tissue determined. Differentially expressed miRNAs (DE-miRNAs) mRNAs (DE-mRNAs) defined by |logFC| > log1.5 P 0.05. Enrichment analyses gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathways performed. Candidate interaction pairs acquired from miRTarBase, network was constructed using Cytoscape Spearman correlation coefficient (r). Results: We identified 19 DE-miRNAs 340 DE-mRNAs. The most enriched GO terms related biological processes cycle, viral process, genome replication. KEGG pathway enrichment analysis suggested these predicted targets associated B. Finally, we found high between miR-4295 ZNF224, which they form axis patients. Conclusions: Our ZNF224 be CHB-GZ.