HBx increases chromatin accessibility and ETV4 expression to regulate dishevelled-2 and promote HCC progression

Zheng, Chuanchao; Liu, Min; Ge, Yanping; Qian, Yanyan; Fan, Hong

doi:10.1038/s41419-022-04563-9

Cited by 22 publications

(17 citation statements)

References 78 publications

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“…Previous studies have proven that NQO1, ETV4, BSG, and HMGA1 are highly expressed in HCC ( Jin et al, 2019 ; Teng et al, 2019 ; Yang et al, 2021 ; Zheng et al, 2022 ). In addition, the upregulation of PBK, BIRC5, PLK1, and EZH2 was also validated in HCC tissues ( Xiao et al, 2019 ; Yang et al, 2019 ; Tian et al, 2020 ; Huang et al, 2021 ; Lin et al, 2021 ; Peng et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have revealed that NQO1 is upregulated and promotes an aggressive phenotype in HCC ( Shimokawa et al, 2020 ; Yang et al, 2021 ; Wang et al, 2022 ). Zheng et al reported that the enhanced expression of ETV4 by HBx may stimulate the metastasis of HCC ( Zheng et al, 2022 ) The literature showed that the interaction between ETV4 and YAP conferred a growth advantage to HCC and had a protumorigenic role ( Xu et al, 2022 ). Some studies have shown that BSG and HMGA1 play significant roles in the development and progression of HCC ( Li et al, 2015 ; Jin et al, 2019 ; Teng et al, 2019 ; Chen et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

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An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning

et al. 2023

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Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment in recent years, there is still an urgent unmet need to explore the underlying mechanisms and novel prognostic markers. Anoikis has received considerable attention because of its involvement in the progression of human malignancies. However, the potential mechanism of anoikis-related genes (ANRGs) involvement in HCC progression remains unclear.Methods: We use comprehensive bioinformatics analyses to determine the expression profile of ANRGs and their prognostic implications in HCC. Next, a risk score model was established by least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Then, the prognostic value of the risk score in HCC and its correlation with clinical characteristics of HCC patients were further explored. Additionally, machine learning was utilized to identify the outstanding ANRGs to the risk score. Finally, the protein expression of DAP3 was examined on a tissue microarray (TMA), and the potential mechanisms of DAP3 in HCC was explored.Results: ANRGs were dysregulated in HCC, with a low frequency of somatic mutations and associated with prognosis of HCC patients. Then, nine ANRGs were selected to construct a risk score signature based on the LASSO model. The signature presented a strong ability of risk stratification and prediction for overall survival in HCC patients.Additionally, high risk scores were closely correlated with unfavorable clinical features such as advanced pathological stage, poor histological differentiation and vascular invasion. Moreover, The XGBoost algorithm verified that DAP3 was an important risk score contributor. Further immunohistochemistry determined the elevated expression of DAP3 in HCC tissues compared with nontumor tissues. Finally, functional analyses showed that DAP3 may promote HCC progression through multiple cancer-related pathways and suppress immune infiltration.Conclusion: In conclusion, the anoikis-based signature can be utilized as a novel prognostic biomarker for HCC, and DAP3 may play an important role in the development and progression of HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning

et al. 2023

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“…HBV‐encoded HBx is an oncogenic protein which could regulate gene transcription 29 . HBx can promote the expression of ETV4 to enhance the invasion and metastasis of HCC cell 30 . HBx also can negatively regulate p53 transcriptional activity to promote cell proliferation 7 .…”

Section: Discussionmentioning

confidence: 99%

“…29 HBx can promote the expression of ETV4 to enhance the invasion and metastasis of HCC cell. 30 HBx also can negatively regulate p53 transcriptional activity to promote cell proliferation. 7 In this study, we found that HBx inhibits the transcription of DCN by interfering the activity of p53.…”

Section: Discussionmentioning

confidence: 99%

HBx downregulated decorin and decorin‐derived peptides inhibit the proliferation and tumorigenicity of hepatocellular carcinoma cells

Gan

et al. 2023

The FASEB Journal

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Hepatitis B virus (HBV) is one of the important risk factors in inducing the occurrence and development of liver cancer, while the mechanism has not been fully clarified. In this study, we found decorin (DCN) was significantly reduced in HBV transgenic cell line HepG2‐4D14 compared to HepG2. The data from hepatocellular carcinoma (HCC) patients indicated that the level of DCN mRNA was significantly lower in tumor tissues than healthy control and positively correlated with the survival of HCC patients. We revealed that HBV HBx can inhibit the transcription of DCN by blocking p53 activity. Functional analysis demonstrated that overexpression of DCN substantially inhibits the proliferation of HCC cells, while knockdown of DCN enhances the proliferation of HCC cells. It is known that DCN could competitively bind to c‐Met to inhibit HGF/c‐Met signaling pathway to inhibit the development of HCC. Therefore, we screened the novel antitumor peptides derived from DCN based on the sequence of DCN and the complex structure of HGF/c‐Met with virtual screening and identified a set of DCN‐derived peptides (DCN‐Ps) which may competitively bind to c‐Met. We found that 5 of peptides can reduce the proliferation and migration of HepG2 cells significantly. Among them, DCN‐P#3 can inhibit the growth of HCC cells both in vitro and in vivo. In conclusion, we discovered that HBV HBx downregulates the expression of DCN, which in turn promotes the proliferation of hepatocytes and the development of HCC. We identified DCN‐derived antitumor peptides which provides the candidates for developing novel drugs against HCC.

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“…1,2 As manifested in clinical practices, hepatitis viral infection is also a critical reason contributing to the poor prognosis of HCC. 3 However, recent studies have reported that infection of the hepatitis virus may contribute to a better response to immunotherapy in HCC patients. 4,5 It is necessary to take viral infection into consideration of evaluating the response to immunotherapy, which is also crucial for treatment strategies in HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Establishment of nucleic acid sensing pathways‐based model in predicting response to immunotherapy and targeted drug in hepatitis virus‐related hepatocellular carcinoma

Peng,

Shi,

Zhang

et al. 2023

Journal of Medical Virology

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Hepatocellular carcinoma (HCC) accounts for 80% of liver cancers, while 70%–80% of HCC developed from chronic liver disease with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as the major etiology. Immunotherapy is assuming a role as a pillar of HCC treatment, but the remarkable immune‐mediated responses are restricted in a minority of patients. Nucleic acid sensing (NAS) pathways are the central pathway of the innate immune system and antiviral immune response to viral infection, but their role in hepatitis virus‐related HCC remains undetermined. In our study, we performed a comprehensive bioinformatics analysis based on transcriptomic data of hepatitis virus related‐HCC tissues collected from multiple public data sets. Two subgroups were validated based on NAS‐related genes in virus‐related HCC patients, which were defined as NAS‐activated subgroups and NAS‐suppressed subgroups based on the expression of NAS‐related genes. On this basis, a NAS‐related risk score (NASRS) predictive model was established for risk stratification and prognosis prediction in the hepatitis virus‐related HCC (TCGA‐LIHC and ICGC cohorts). The predictive values of the NASRS in prognosis and immunotherapy were also verified in multiple data sets. A nomogram was also established to facilitate the clinical use of NASRS and demonstrate its effectiveness through different approaches. Additionally, six potential drugs binding to the core target of the NAS signature were predicted via molecular docking strategy. We subsequently evaluated the cytotoxic capabilities of potential drug in vitro and in vivo. Based on these results, we conclude that the NASRS model could serve as a power prognostic biomarker and predict responses to immunotherapy, which is meaningful in clinical decision‐making of hepatitis virus‐related HCC patients.

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HBx increases chromatin accessibility and ETV4 expression to regulate dishevelled-2 and promote HCC progression

Cited by 22 publications

References 78 publications

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning

HBx downregulated decorin and decorin‐derived peptides inhibit the proliferation and tumorigenicity of hepatocellular carcinoma cells

Establishment of nucleic acid sensing pathways‐based model in predicting response to immunotherapy and targeted drug in hepatitis virus‐related hepatocellular carcinoma

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