ArticleOncogene2019
HBx regulates transcription factor PAX8 stabilization to promote the progression of hepatocellular carcinoma.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- Aurora kinase a phosphorylates and stabilizes UHRF1 to maintain DNA methylation and prostate cancer cell survival.Epigenetics · 2026Article
- Article
- The Ubiquitin-Proteasome System in Hepatitis B Virus Infection and Hepatocarcinogenesis: Viral Manipulation and Therapeutic Targets.Journal of microbiology and biotechnology · 2025Review
- The potential role of PAX5 and PAX8 in regulating telomerase activity: a narrative mini-review.Molecular biology reports · 2025Review
- Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Transcription factor E4F1 as a regulator of cell life and disease progression.Science advances · 2023Review
- HBx promotes hepatocellular carcinoma progression by repressing the transcription level of miR-187-5p.Aging · 2023Article
- Advances in experimental animal models of hepatocellular carcinoma.Cancer medicine · 2023Review
- Integrated analysis of intratumoral biomarker and tumor-associated macrophage to improve the prognosis prediction in cancer patients.BMC cancer · 2023Article
- Aerobic glycolysis enhances HBx-initiated hepatocellular carcinogenesis via NF-κBp65/HK2 signalling.Journal of experimental & clinical cancer research : CR · 2022Article
- VCP interaction with HMGB1 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway.Journal of translational medicine · 2022Article
- NAFLD and HBV interplay - related mechanisms underlying liver disease progression.Frontiers in immunology · 2022Review
- HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the GAutophagy · 2021Article
- HBx promotes hepatocarcinogenesis by enhancing phosphorylation and blocking ubiquitinylation of UHRF2.Hepatology international · 2021Article
- Secreted TRAIL gene-modified adipose-derived stem cells exhibited potent tumor-suppressive effect in hepatocellular carcinoma cells.Immunity, inflammation and disease · 2021Article
- The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis.Frontiers in immunology · 2021Review
- MACC1-AS1 promotes hepatocellular carcinoma cell invasion and proliferation by regulating PAX8.Aging · 2020Article
- Kelch-like protein 14 promotes proliferation and migration of ovarian cancer cells.International journal of clinical and experimental pathology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription factor PAX8 expression is upregulated in several types of cancers. However, little is known about the function of PAX8 in the progression of hepatoma and its regulatory mechanisms. Here, we show that PAX8 silencing inhibits the proliferation and clonogenicity of hepatoma cells and its growth in vivo. The HBV X protein (HBx) does not directly interacts, but stabilizes PAX8 by inhibiting proteasome-dependent ubiquitination and degradation. Furthermore, the E3 ubiquitin ligase complex component Skp2 through its LRR domain directly interacts with the Prd domain of PAX8 and targets PAX8 by recognizing its lysine 275 for ubiquitination and degradation in hepatoma cells. In addition, HBx directly interacts and is colocalized with Skp2 to inhibit its recognition and subsequent ubiquitination and degradation of PAX8 in hepatoma cells. Moreover, HBx upregulates the expression and phosphorylation of Aurora A, a serine-threonine kinase, which interacts with and phosphorylates PAX8 at S209 and T277, compromising the Skp2-recognized PAX8 ubiquitination and destabilization. Thus, HBx stabilizes PAX8 protein by inhibiting the Skp2 targeted PAX8 ubiquitination and enhancing the Aurora A-mediated its phosphorylation, contributing to the progression of hepatoma. Our findings suggest that PAX8 may a new target for design of therapies and uncover new insights into the pathogenesis of hepatoma.
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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.