Frontiers in immunology · 2026
Screening and validating HBV mother-to-child transmission-related lncRNAs based on the lncRNA-mRNA co-expression network.
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He Quan, Zheng Chunyan, Zhang Jiawei, Su Yongjian, Li Jialing, Chen Shiyi, Cui Haichen, Zeng Ting, Zou Xiong, Li Hai
Аннотация
BACKGROUND: Despite standard immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccination, a proportion of infants born to hepatitis B surface antigen (HBsAg)-positive mothers still experience mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The molecular mechanisms underlying immunoprophylaxis failure remain incompletely understood. Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulators of antiviral immune responses; however, their role in HBV MTCT has not been fully elucidated.
METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from infants born to HBsAg-positive mothers with either successful or failed MTCT prevention, as well as from healthy controls. Whole-transcriptome RNA sequencing was performed to identify differentially expressed mRNAs and lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the associated biological functions and pathways. An lncRNA-mRNA co-expression network was constructed to identify potential regulatory relationships. Key genes were further validated using real-time quantitative PCR (RT-qPCR).
RESULTS: A total of 2,647 differentially expressed mRNAs and 1,082 differentially expressed lncRNAs were identified between the MTCT prevention failure group and the successful prevention group. Functional enrichment analysis revealed that these genes were mainly involved in immune-related biological processes, including cytokine-mediated signaling, neutrophil activation, and innate immune responses. KEGG pathway analysis demonstrated significant enrichment in pathways related to hepatitis B, MAPK signaling, and NOD-like receptor signaling. The lncRNA-mRNA co-expression network identified 440 potential regulatory interactions associated with MTCT blockade failure. RT-qPCR validation demonstrated that HRAS expression was significantly downregulated in the MTCT blockade failure group, whereas ICAM1, NAMPT, and SOD2 were significantly upregulated compared with healthy controls.
CONCLUSION: Our findings reveal distinct transcriptomic profiles associated with HBV MTCT and suggest that dysregulated immune-related genes and lncRNA-mRNA regulatory networks may be associated with MTCT prevention failure. In particular, altered expression of HRAS, ICAM1, NAMPT, and SOD2 may represent candidate biomarkers associated with HBV MTCT related to HBV transmission and immune responses in infants. These findings provide preliminary insights into the molecular characteristics of HBV MTCT and may help guide future mechanistic and clinical studies.
METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from infants born to HBsAg-positive mothers with either successful or failed MTCT prevention, as well as from healthy controls. Whole-transcriptome RNA sequencing was performed to identify differentially expressed mRNAs and lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the associated biological functions and pathways. An lncRNA-mRNA co-expression network was constructed to identify potential regulatory relationships. Key genes were further validated using real-time quantitative PCR (RT-qPCR).
RESULTS: A total of 2,647 differentially expressed mRNAs and 1,082 differentially expressed lncRNAs were identified between the MTCT prevention failure group and the successful prevention group. Functional enrichment analysis revealed that these genes were mainly involved in immune-related biological processes, including cytokine-mediated signaling, neutrophil activation, and innate immune responses. KEGG pathway analysis demonstrated significant enrichment in pathways related to hepatitis B, MAPK signaling, and NOD-like receptor signaling. The lncRNA-mRNA co-expression network identified 440 potential regulatory interactions associated with MTCT blockade failure. RT-qPCR validation demonstrated that HRAS expression was significantly downregulated in the MTCT blockade failure group, whereas ICAM1, NAMPT, and SOD2 were significantly upregulated compared with healthy controls.
CONCLUSION: Our findings reveal distinct transcriptomic profiles associated with HBV MTCT and suggest that dysregulated immune-related genes and lncRNA-mRNA regulatory networks may be associated with MTCT prevention failure. In particular, altered expression of HRAS, ICAM1, NAMPT, and SOD2 may represent candidate biomarkers associated with HBV MTCT related to HBV transmission and immune responses in infants. These findings provide preliminary insights into the molecular characteristics of HBV MTCT and may help guide future mechanistic and clinical studies.