ArticleOncogene2020
TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Multiplexed iPSC platform for advanced NK cell immunotherapies.Cell reports. Medicine · 2025Review
- An overview of hepatitis B virus in gastric carcinogenesis: from clinical association to molecular mechanisms.Infectious agents and cancer · 2025Review
- HBV promotes epithelial-mesenchymal transition in HCC and liver fibrosis through JNK-mediated autophagy.Hepatology communications · 2025Article
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 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
- Immunomodulatory behavior of CircRNAs in tumor microenvironment.Oncology research · 2025Review
- Insight into the mechanisms regulating liver cancer stem cells by hepatitis B virus X protein.Infectious agents and cancer · 2024Review
- Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells.Cell stem cell · 2024Article
- Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression.Frontiers of medicine · 2024Review
- Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis.Frontiers of medicine · 2024Article
- The Role of Epithelial Cell Adhesion Molecule Cancer Stem Cell Marker in Evaluation of Hepatocellular Carcinoma.Medicina (Kaunas, Lithuania) · 2024Article
- Article
- Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma.Frontiers in oncology · 2024Review
- Exploring the hepatoprotective properties of citronellol:Open life sciences · 2024Article
- Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Review
- JNK/c-Jun pathway activation is essential for HBx-induced IL-35 elevation to promote persistent HBV infection.Journal of clinical laboratory analysis · 2023Article
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.Cell death & disease · 2022Article
- Hepatitis B virus X protein mediated epigenetic alterations in the pathogenesis of hepatocellular carcinoma.Hepatology international · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-β1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-β1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-β1 than in those with high HBx or high TGF-β1 and the double-low-expression group. HBx and TGF-β1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-β1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial-mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-β1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-β1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-β1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.
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