HBV Integration-mediated Cell Apoptosis in HepG2.2.15.

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern, with Hepatitis B virus (HBV) infection being a key risk factor.
• The precise mechanisms by which HBV DNA integration influences host cell behavior in HCC pathogenesis are not fully elucidated.

Purpose of the Study:

• To investigate the impact of HBV integration on host cell functions at the genomic and transcriptomic levels in an HCC cell line.
• To identify specific host genes targeted by HBV integration and assess their role in HCC progression.

Main Methods:

• Utilized HepG2.2.15 cells (HCC cells with stable HBV expression) and compared them to HepG2 cells.
• Performed HBV capture sequencing at both genomic and transcriptomic levels.
• Conducted RNA expression sequencing and gene knockdown experiments.

Main Results:

• HBV integration targeted genes including CAMSAP2, CCDC12, DPP7, and OR4F3, altering their expression.
• DPP7 was uniquely targeted by HBV integration within its exon, showing downregulated expression in HepG2.2.15 cells.
• Knockdown of DPP7 in HepG2 cells increased apoptosis via the Bax/Bcl2 ratio.

Conclusions:

• HBV integration into the DPP7 gene is implicated in HCC pathogenesis.
• DPP7 downregulation due to HBV integration contributes to increased apoptosis in liver cancer cells.