Hepatitis B x antigen (HBx) is an important therapeutic target in the pathogenesis of hepatocellular carcinoma

Medhat, Arvin; Arzumanyan, Alla; Feitelson, Mark A.

doi:10.18632/oncotarget.28077

Cited by 15 publications

(11 citation statements)

References 96 publications

(128 reference statements)

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“…Although the innate immune system plays a central role in targeting HBV, the virus triggers only a small innate response and has evolved a variety of escape strategies to block the antiviral response in host cells. As a viral nonstructural protein, HBX is considered a vital therapeutic target for HBV infection because the viral protein not only contributes to the replication of the virus and participates in the development of liver cancer induced by HBV, but also protects HBV-infected cells from immune-mediated clearance ( 22 , 159 ). In the present review, we summarized the recent progress regarding the role and associated mechanisms of HBX in PPR signaling during HBV infection.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

et al. 2022

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As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.

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Section: Discussionmentioning

confidence: 99%

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

et al. 2022

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“…Proteins frequently perform their functions by forming complexes. HBx induces promiscuous transactivation by means of protein-protein interaction [ 33 ]. To gain a better understanding of how these distinct molecules contribute to the prevalence of HBV-related HCC, the physical and functional interactions between these proteins were analyzed and 20 pivotal molecules (hub genes) that contribute significantly to the interaction were screened using the STRING database.…”

Section: Discussionmentioning

confidence: 99%

Significance of Identifying Key Genes Involved in HBV-Related Hepatocellular Carcinoma for Primary Care Surveillance of Patients with Cirrhosis

et al. 2022

Genes

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Cirrhosis is frequently the final stage of disease preceding the development of hepatocellular carcinoma (HCC) and is one of the risk factors for HCC. Preventive surveillance for early HCC in patients with cirrhosis is advantageous for achieving early HCC prevention and diagnosis, thereby enhancing patient prognosis and reducing mortality. However, there is no highly sensitive diagnostic marker for the clinical surveillance of HCC in patients with cirrhosis, which significantly restricts its use in primary care for HCC. To increase the accuracy of illness diagnosis, the study of the effective and sensitive genetic biomarkers involved in HCC incidence is crucial. In this study, a set of 120 significantly differentially expressed genes (DEGs) was identified in the GSE121248 dataset. A protein–protein interaction (PPI) network was constructed among the DEGs, and Cytoscape was used to extract hub genes from the network. In TCGA database, the expression levels, correlation analysis, and predictive performance of hub genes were validated. In total, 15 hub genes showed increased expression, and their positive correlation ranged from 0.80 to 0.90, suggesting they may be involved in the same signaling pathway governing HBV-related HCC. The GSE10143, GSE25097, GSE54236, and GSE17548 datasets were used to investigate the expression pattern of these hub genes in the progression from cirrhosis to HCC. Using Cox regression analysis, a prediction model was then developed. The ROC curves, DCA, and calibration analysis demonstrated the superior disease prediction accuracy of this model. In addition, using proteomic analysis, we investigated whether these key hub genes interact with the HBV-encoded oncogene X protein (HBx), the oncogenic protein in HCC. We constructed stable HBx-expressing LO2-HBx and Huh-7-HBx cell lines. Co-immunoprecipitation coupled with mass spectrometry (Co-IP/MS) results demonstrated that CDK1, RRM2, ANLN, and HMMR interacted specifically with HBx in both cell models. Importantly, we investigated 15 potential key genes (CCNB1, CDK1, BUB1B, ECT2, RACGAP1, ANLN, PBK, TOP2A, ASPM, RRM2, NEK2, PRC1, SPP1, HMMR, and DTL) participating in the transformation process of HBV infection to HCC, of which 4 hub genes (CDK1, RRM2, ANLN, and HMMR) probably serve as potential oncogenic HBx downstream target molecules. All these findings of our study provided valuable research direction for the diagnostic gene detection of HBV-related HCC in primary care surveillance for HCC in patients with cirrhosis.

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“…[ 1 , 2 ]. HBx [ 20 , 21 ] and YAP [ 22 , 23 ] proteins have been reported to be involved in HBV-related HCC occurrence [ 12 ]. However, the expression patterns in HCC and peritumor tissue, and their relationship with clinical information including tumor characteristics, tumor marker, and prognosis have not been examined.…”

Section: Discussionmentioning

confidence: 99%

HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma

Oda

Kamimura

Shibata

et al. 2022

Biochemistry and Biophysics Reports

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Hepatitis B x antigen (HBx) is an important therapeutic target in the pathogenesis of hepatocellular carcinoma

Cited by 15 publications

References 96 publications

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

Significance of Identifying Key Genes Involved in HBV-Related Hepatocellular Carcinoma for Primary Care Surveillance of Patients with Cirrhosis

HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma

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