Viral-human chimeric transcript predisposes risk to liver cancer development and progression

Area of Science:

• Molecular Biology
• Hepatology
• Oncology

Background:

• The role of hepatitis B virus (HBV) integration in hepatocellular carcinoma (HCC) development is not fully understood.
• Identifying specific viral-host interactions is crucial for understanding HCC pathogenesis.

Purpose of the Study:

• To investigate the functional consequences of HBV integration in HCC.
• To identify novel viral-human fusion transcripts and their role in liver cancer.

Main Methods:

• Transcriptome sequencing of HBV-positive HCC cell lines.
• Detection of viral-human gene fusions.
• Functional assays in cell lines and transgenic mouse models.
• Analysis of patient tumor samples.

Main Results:

• Discovery of a tumor-promoting chimeric transcript, HBx-LINE1, formed by HBV-human gene fusion.
• HBx-LINE1 detected in 23.3% of HBV-associated HCC tumors, correlating with poorer patient survival.
• HBx-LINE1 transgenic mice exhibited increased susceptibility to chemically induced liver tumors.
• HBx-LINE1 expression was shown to activate Wnt signaling by affecting β-catenin transactivity.

Conclusions:

• A novel viral-human chimeric fusion transcript, HBx-LINE1, acts as a long noncoding RNA promoting HCC.
• HBx-LINE1 represents a potential biomarker for HCC prognosis and a therapeutic target.