<scp>HB</scp>x triggers either cellular senescence or cell proliferation depending on cellular phenotype

Idrissi, Manale El; Hachem, Hilal; Koering, Catherine; Merle, Philippe; Thénoz, Morgan; Mortreux, Franck; Wattel, Éric

doi:10.1111/jvh.12450

Cited by 15 publications

(15 citation statements)

References 44 publications

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“…This particular protein has been shown to inhibit p53 activity, binding to the C terminus of p53, thereby blocking apoptosis 30 . Accordingly, HBx protein exerts a pro‐senescent role, based upon increased p16 (INK4a) and p21 (Waf1/Cip1) expression and a decreased Rb phosphorylation status 31 . Extracted results confirmed that HBx C‐terminal mutants can trigger cellular senescence in primary MRC5 cells, malignant liver cells Huh7 and SK‐Hep1.…”

Section: Interplay Between Hbv and Cellular Senescencementioning

confidence: 77%

“…Extracted results confirmed that HBx C‐terminal mutants can trigger cellular senescence in primary MRC5 cells, malignant liver cells Huh7 and SK‐Hep1. In contrast, these mutants promoted the proliferation of HepG2 malignant liver cells 31 . Excessive secretion of SASP components has also been reported in chronic hepatitis B, while HBV infection has been associated with elevated levels of angiogenin‐2.…”

Section: Interplay Between Hbv and Cellular Senescencementioning

confidence: 95%

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Cellular senescence and hepatitis B‐related hepatocellular carcinoma: An intriguing link

Karakousis

Papatheodoridi

Chatzigeorgiou

et al. 2020

Liver International

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Chronic hepatitis B is mainly responsible for the morbidity and mortality from hepatitis B virus (HBV)‐related complications, including hepatocellular carcinoma (HCC) and decompensated cirrhosis. Hepatocellular carcinoma remains the main challenge in the management of not only undiagnosed and/or untreated but also diagnosed and treated patients with chronic HBV infection, as its incidence decreases but is not eliminated even after many years of effective anti‐HBV therapy. The exact mechanisms used by HBV to cause malignant transformation remain uncertain, although much of the available data are in favour of a pathogenetic role of HBx protein. Senescence is a cellular state, in which cells lose their ability to proliferate. This biological mechanism may function in a dual mode, namely being both cancer‐protective as a result of reduced cellular proliferation, but also cancer‐enhancing as a result of modulation of the tissular microenvironment by immune cells during persistent accumulation of senescent cells. Protein X of HBV protein exhibits many similarities in terms of the implemented mechanisms of action and pathways related to the biological process of cellular senescence. Concurrently, insufficient clearance of both senescent and precancerous hepatocytes combined with inadequate immune surveillance as a result of immunosenescence caused by chronic HBV infection may lead to hepatocarcinogenesis. Thus, the effect of HBV seems to be critical as a connecting link between cellular senescence and development of HCC. An ongoing research is underway towards identifying and validating markers of hepatocyte senescence, which could improve the landscape for evaluation of chronic liver disease, thereby providing valuable information in terms of HBV‐related carcinogenesis.

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Section: Interplay Between Hbv and Cellular Senescencementioning

confidence: 77%

Section: Interplay Between Hbv and Cellular Senescencementioning

confidence: 95%

Cellular senescence and hepatitis B‐related hepatocellular carcinoma: An intriguing link

Karakousis

Papatheodoridi

Chatzigeorgiou

et al. 2020

Liver International

View full text Add to dashboard Cite

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“…3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT; Sigma‐Aldrich) assay was performed as previously described . Cells in 96‐well plate were transfected and allowed to grow for 4 days and then treated with 1 mg mL −1 MTT solution for 4 hours at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; Sigma-Aldrich) assay was performed as previously described. [27][28][29]…”

Section: Cell Proliferation (Mtt) Assaymentioning

confidence: 99%

A comparative study of hepatitis B virus X protein mutants K130M, V131I and KV130/131MI to investigate their roles in fibrosis, cirrhosis and hepatocellular carcinoma

Siddiqui

Farooqui

Azam

et al. 2017

Journal of Viral Hepatitis

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Hepatitis B virus (HBV) genomic mutations A1762T, G1764A and AG1762/1764TA cause production of HBV X protein (HBx) mutants, namely K130M, V131I and KV130/131MI. These mutations are important biomarkers for the development of cirrhosis and hepatocellular carcinoma (HCC) in chronic HBV patients. This study comparatively analyses the impact of intracellular expression of HBx mutants on HCC cell line Huh7. It was found that expression of KV130/131MI induced: cell proliferation, altered expression of cell cycle regulatory genes in favour of cell proliferation, intracellular reactive oxygen species (ROS) production and mitochondrial depolarization. KV130/131MI may be directly involved in host cell proliferation and hepatocarcinogenesis via altering expression of cell cycle regulatory genes. KV130/131MI may also play pivotal roles in fibrosis and cirrhosis via inducing ROS production and mitochondrial depolarization. Furthermore, these might be the possible reasons for higher occurrence of AG1762/1764TA as compared to A1762T and G1764A in cirrhosis and HCC patients.

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“…Several studies have demonstrated that HCC-associated HBx mutants more strongly promote oncogenesis than intact HBx 11 . For example, HBx mutants with a C-terminal truncation promote or inhibit cell proliferation in a manner that depends on deletion sites 12 . However, the molecular mechanisms by which the functions of HBx are altered in the presence of HBx mutations and cause the promotion of HBV-related hepatocarcinogenesis have not yet been elucidated in detail.…”

Section: Introductionmentioning

confidence: 99%

Contribution of C1485T mutation in the HBx gene to human and murine hepatocarcinogenesis

Hagiwara

Nishida

Park

et al. 2017

Sci Rep

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Although Hepatitis B virus (HBV) X gene mutations are frequently detected in HBV-related human hepatocellular carcinoma (HCC) patients, causative HBx mutations in the development of HCC have not yet been determined. We herein identified C1485T and C1653T mutations in the HBx gene as independent risk of HCC for HBV through the analysis using serum from chronic hepatitis B patients. We generated transgenic mice expressing wild-type (WT-HBxTg) and mutant (C1485T-HBxTg) HBx to assess the carcinogenic potential of mutated HBx. C1485T-HBxTg mice were more susceptible to diethylnitrosamine-induced hepatocarcinogenesis than WT-HBxTg mice and control non-Tg mice. The promotion of hepatocarcinogenesis in C1485T-HBxTg mice was accompanied by the activation of β-catenin and Jun N-terminal kinase (JNK) signaling pathways as well as the production of reactive oxygen species, whereas the activation of nuclear factor-kappa B in the livers of C1485T-HBxTg mice was attenuated. These results demonstrate that the HBx C1485T mutation contributes to human and murine hepatocarcinogenesis.

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HBx triggers either cellular senescence or cell proliferation depending on cellular phenotype

Cited by 15 publications

References 44 publications

Cellular senescence and hepatitis B‐related hepatocellular carcinoma: An intriguing link

Cellular senescence and hepatitis B‐related hepatocellular carcinoma: An intriguing link

A comparative study of hepatitis B virus X protein mutants K130M, V131I and KV130/131MI to investigate their roles in fibrosis, cirrhosis and hepatocellular carcinoma

Contribution of C1485T mutation in the HBx gene to human and murine hepatocarcinogenesis

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