Comprehensive Analysis of the mRNA-lncRNA Co-expression Profile and ceRNA Networks Patterns in Chronic Hepatitis B

Abstract

Background: Long non-coding RNAs (lncRNAs) are emerging as important regulators in the modulation of virus infection by targeting mRNA transcription. However, their roles in chronic hepatitis B (CHB) remain to be elucidated. Objective: The study aimed to explore the lncRNAs and mRNA expression profiles in CHB and asymptomatic HBsAg carriers (ASC) and construct mRNA-lncRNA co-expression profile and ceRNA networks to identify the potential targets of diagnosis and treatment in CHB. Methods: We determined the expression profiles of lncRNAs and mRNAs in CHB and ASC using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore their function. We also constructed coexpression, cis-regulatory, and competing endogenous RNA (ceRNA) networks with bioinformatics methods. Results: We identified 1634 mRNAs and 5550 lncRNAs that were differentially expressed between CHB and ASC. Significantly enriched GO terms and pathways were identified, many of which were linked to immune processes and inflammatory responses. Co-expression analysis showed 1196 relationships between the top 20 up/downregulated lncRNAs and mRNA, especially 213 lncRNAs interacted with ZFP57. The ZFP57-specific ceRNA network covered 3 lncRNAs, 5 miRNAs, and 17 edges. Cis-correlation analysis showed that lncRNA T039096 was paired with the most differentially expressed gene, ZFP57. Moreover, by expending the clinical samples size, the qRT-PCR results showed that the expression of ZFP57 and T039096 increased in CHB compared to ASC. Conclusion: Our study provides insights into the roles of mRNA and lncRNA networks in CHB, highlighting potential applications of lncRNA-T039096 and mRNA-ZFP57 for diagnosis and treatment.