HBx Protein in Hepatitis B Virus-Related Hepatocellular Carcinoma:PathogenicMechanisms and Emerging InterventionsOA
Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide,most commonly driven by chronic hepatitis B virus(HBV)infection.The HBV X protein(HBx)plays a central role in hepatocarcinogenesis by regulating transcription,signal transduction,epigenetic modification,and interactions with noncoding RNAs.This reviewsummarizes current advances inHBx-mediated signaling pathways andmutation-specific functions,highlighting its potential as a prognostic biomarker and therapeutic target,and providing insights for future strategies in HCC treatment andHBV eradication.Activation of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),cAMP response element binding protein/activating transcription factor(CREB/ATF),and phosphatidylinositol 3′-kinase/AKT serine-threonine protein kinase family(PI3K/Akt)pathways by HBx promotes tumor proliferation,epithelial-mesenchymal transition,and immune evasion.Mutation-and truncation-specific variants of HBx,such as C1485T,C1653T,and K130M/V131I,further enhance oxidative stress,inflammatory signaling,and chemoresistance,contributing to poor prognosis.Emerging preclinical evidence indicates that natural compounds,including asiatic acid,sphondin,and rapamycin,can suppressHBx stability and transcriptional activity,offering novel antiviral and antitumor strategies.Understanding HBx-drivenmolecularmechanisms andmutation-specific effects may guide the development of precise diagnostic,prognostic,and therapeutic approaches for HBV-related HCC.
Chung-Che Tsai;Chih-Hung Lin;Katherine Lin;Jia Hong Hubert Chen;Ying Jie Celia Chen;Ilyssa Ting-Ying Chang;Hsu-Hung Chang;Jin-Yin Chang;Tin-Yi Chu;Po-Chih Hsu;Chan-Yen Kuo
Department of Research,Taipei Tzu Chi Hospital,The Buddhist Tzu Chi Medical Foundation,New Taipei City,231,Taiwan,ChinaDepartment of Internal Medicine,Cathay General Hospital,Taipei,106,Taiwan,ChinaTaipei Fuhsing Private School,Taipei,106,Taiwan,China Department of Dentistry,Taipei Tzu Chi Hospital,The Buddhist Tzu Chi Medical Foundation,New Taipei City,231,Taiwan,ChinaDepartment of Dentistry,Taipei Tzu Chi Hospital,The Buddhist Tzu Chi Medical Foundation,New Taipei City,231,Taiwan,China Taipei American School,Taipei,111,Taiwan,ChinaDepartment of Dentistry,Taipei Tzu Chi Hospital,The Buddhist Tzu Chi Medical Foundation,New Taipei City,231,Taiwan,China Taipei American School,Taipei,111,Taiwan,ChinaTaipei Fuhsing Private School,Taipei,106,Taiwan,China Department of Dentistry,Taipei Tzu Chi Hospital,The Buddhist Tzu Chi Medical Foundation,New Taipei City,231,Taiwan,ChinaDivision of Nephrology,Department of Internal Medicine,Sijhih Cathay General Hospital,New Taipei City,221,Taiwan,ChinaDepartment of Medical Research,Cathay General Hospital,Taipei,106,Taiwan,ChinaInstitute of Oral Medicine and Materials,College of Medicine,Tzu Chi University,Hualien,970,Taiwan,ChinaDepartment of Dentistry,Taipei Tzu Chi Hospital,The Buddhist Tzu Chi Medical Foundation,New Taipei City,231,Taiwan,China Institute of Oral Medicine and Materials,College of Medicine,Tzu Chi University,Hualien,970,Taiwan,ChinaInstitute of Oral Medicine and Materials,College of Medicine,Tzu Chi University,Hualien,970,Taiwan,China
医药卫生
Hepatitis B virus X proteinhepatocellular carcinomahepatitis B virus X mutationstumor microenvironmentsignal transduction pathways
《BIOCELL》 2026 (3)
P.1-23,23
funded by grants fromthe Cathay General Hospital in Taipei(CGH-MR-A11326 to C.-H.L.).
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