ArticleOncotarget2016
C-terminal truncated hepatitis B virus X protein promotes hepatocellular carcinogenesis through induction of cancer and stem cell-like properties.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 59 citations in OpenAlex.
- Promiscuous Metal Site in Hepatitis B Virus X Protein Binds an Fe-S Cluster.bioRxiv : the preprint server for biology · 2026Article
- Review
- The interplay between hepatitis B virus and antitumor drugs in the treatment of hepatocellular carcinoma.Clinical and experimental medicine · 2025Review
- HBx mutant-regulated RPL13AP25 mediates suboptimal virological response to entecavir and HCC progression.Cancer cell international · 2025Article
- Defective but tumorigenic: the evolutionary and functional roles of mutated oncoviruses.FEMS microbiology reviews · 2025Review
- HBV-Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Targeting Hepatic Cancer Stem Cells (CSCs) and Related Drug Resistance by Small Interfering RNA (siRNA).Cell biochemistry and biophysics · 2024Review
- Insight into the mechanisms regulating liver cancer stem cells by hepatitis B virus X protein.Infectious agents and cancer · 2024Review
- Review
- The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.Biomarker research · 2024Review
- Reactivation of hepatitis B virus infection - an important aspect of multifaceted problem.World journal of gastroenterology · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression.Frontiers of medicine · 2024Review
- Overview of hepatocellular carcinoma: from molecular aspects to future therapeutic options.Cell adhesion & migration · 2023Review
- A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer.Cell communication and signaling : CCS · 2023Review
- Hepatitis B Virus-Associated Hepatocellular Carcinoma.Viruses · 2022Review
- Hepatitis B virus DNA integration as a novel biomarker of hepatitis B virus-mediated pathogenetic properties and a barrier to the current strategies for hepatitis B virus cure.Frontiers in microbiology · 2022Review
- Article
- Review
- Regulators of liver cancer stem cells.World journal of stem cells · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor relapse after chemotherapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive initial treatment. Chronic infection with hepatitis B virus (HBV) has long been linked to the development of HCC. Upon infection, random HBV genome integration can lead to truncation of hepatitis B virus X (HBx) protein at the C-terminus. The resulting C-terminal-truncated HBx (HBx-ΔC) was previously shown to confer enhanced invasiveness and diminished apoptotic response in HCC cells. Here, we found HBx-ΔC to promote the appearance of a CD133 liver CSC subset and confer cancer and stem cell-like features in HCC. HBx-ΔC was exclusively detected in HCC cell lines that were raised from patients presented with a HBV background with concomitant CD133 expression. Stable overexpression of the naturally occurring HBx-ΔC mutants, HBx-Δ14 or HBx-Δ35, in HCC cells Huh7 and immortalized normal liver cells MIHA resulted in a significant increase in the cells ability to self-renew, resist chemotherapy and targeted therapy, migrate and induce angiogenesis. MIHA cells with the mutants stably overexpressed also resulted in the induction of CD133, mediated through STAT3 activation. RNA sequencing profiling of MIHA cells with or without HBx-ΔC mutants stably overexpressed identified altered FXR activation. This, together with rescue experiments using a selective FXR inhibitor suggested that C-terminal truncated HBx can mediate cancer stemness via FXR activation. Collectively, we find C-terminal truncated HBx mutants to confer cancer and stem cell-like features in vitro and to play an important role in driving tumor relapse in HCC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.