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Updated: May 14, 2025

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
CircBRWD1 promotes hepatitis B virus replication and hepatocellular carcinoma progression by regulating the
Jiabao Geng1, Fei Huang2, Qiannan Liu3
1Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China; Department of Infectious Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210002, China.
Abstract:
Hepatocellular carcinoma (HCC), primarily caused by chronic hepatitis B virus (HBV) infection, remains a leading cause of liver cancer worldwide. Despite advances in antiviral therapies, persistent HBV replication, mediated by covalently closed circular DNA (cccDNA), contributes to poor prognoses and frequent recurrence of HCC. This study investigates for the first time the role of circular RNA circBRWD1 in HBV-related HCC, aiming to elucidate its function and regulatory mechanism in HBV replication and hepatocarcinogenesis. Results showed that circBRWD1 was significantly overexpressed in HBV-positive HCC tissues and cell lines compared to HBV-negative controls and promoted HBV replication by increasing cccDNA accumulation. Silencing circBRWD1 markedly reduced the levels of HBV DNA, HBV surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV core antigen (HBcAg), indicating its critical role in HBV replication. Functionally, circBRWD1 knockdown led to reduced cell proliferation, colony formation, and migration while increasing apoptosis in HCC cells. Mechanistic studies revealed that circBRWD1 acts as a sponge for miR-513a-5p, thereby upregulating TNPO1, a key player in promoting HCC malignancy. Rescue experiments confirmed that TNPO1 overexpression reversed the effects of circBRWD1 depletion, restoring cell proliferation, migration, and HBV replication. Additionally, circBRWD1 depletion significantly reduced tumor growth with reduced expression of TNPO1 and increased miR-513a-5p levels in a mouse xenograft model. Collectively, this study identifies circBRWD1 as a key oncogenic circRNA that facilitates HBV replication and HCC progression via the miR-513a-5p/TNPO1 axis. Targeting circBRWD1 may offer a novel therapeutic strategy for HBV-related HCC, potentially addressing the challenge of HBV persistence and improving patient outcomes.
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