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Published on: May 10, 2022
Hepatocellular carcinoma progression mediated by hepatitis B virus-encoded circRNA HBV_circ_1 through interaction
1School of Biology & Basic Medical Science, Soochow University, Suzhou 215123, China.
Insights
Hepatitis B virus (HBV) produces a novel circular RNA (circRNA), HBV_circ_1, which promotes hepatocellular carcinoma (HCC) progression by interacting with CDK1. This finding offers a new therapeutic target for HBV-related liver cancer.
Area of Science:
- Hepatology
- Molecular Biology
- Oncology
Background:
- Hepatitis B virus (HBV) produces circular RNAs (circRNAs) with largely unknown functions.
- Hepatocellular carcinoma (HCC) is a major global health concern, often linked to HBV infection.
Purpose of the Study:
- To identify and characterize novel HBV-derived circRNAs in HCC.
- To investigate the role of HBV_circ_1 in HCC development and progression.
- To explore the molecular mechanism of HBV_circ_1 in HCC.
Main Methods:
- Identification of HBV_circ_1 in HBV-positive cells and HCC tissues.
- Microarray analysis of HCC samples.
- In vitro cell proliferation, migration, invasion, and apoptosis assays.
- In vivo tumor growth studies.
- Interaction studies between HBV_circ_1 and CDK1.
Main Results:
- A novel circRNA, HBV_circ_1, was identified and found to be upregulated in HCC tissues.
- Higher HBV_circ_1 levels correlated with lower patient survival rates.
- HBV_circ_1 enhanced HCC cell proliferation, migration, invasion, and inhibited apoptosis in vitro.
- HBV_circ_1 expression increased tumor size in vivo.
- HBV_circ_1 interacts with CDK1 to promote cell proliferation.
Conclusions:
- HBV_circ_1 is a novel oncogenic circRNA produced by HBV that promotes HCC progression.
- The interaction between HBV_circ_1 and CDK1 is a key mechanism driving HCC.
- HBV_circ_1 represents a potential therapeutic target for HBV-related HCC.
Abstract:
Hepatitis B virus (HBV) produces circular RNA (circRNA), whose functions have not yet been clearly elucidated. In this study, a novel circRNA HBV_circ_1 produced by HBV was identified in HBV-positive HepG2.2.15 cells and HBV-related hepatocellular carcinoma (HCC) tissue (HCCT). Microarray analysis of 68 HCCT samples showed that HBV_circ_1 abundance was significantly higher than that in paracancerous tissues. In addition, survival rate of HBV_circ_1-positive patients was significantly lower compared with HBV_circ_1-negative patients. Transient expression indicated that HBV_circ_1 enhanced cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Furthermore, ectopical HBV_circ_1 expression increased tumor size in vivo. HBV_circ_1 was confirmed to interact with cyclin-dependent kinase 1 (CDK1) to regulate cell proliferation. These results suggest that HCC progression may be promoted by interaction of HBV_circ_1 with CDK1. Our data not only showed a novel clue to understand carcinogenesis and progress of HBV-related HCC but also provided a new target for the development of therapeutic drugs.
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