ArticleNucleic acids research2022
High mobility group AT-hook 1 (HMGA1) is an important positive regulator of hepatitis B virus (HBV) that is reciprocally upregulated by HBV X protein.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Natural products targeting hepatitis B virus X protein and HBx-associated pathways in HBV-related hepatocellular carcinoma: mechanisms and therapeutic potential.Pharmaceutical biology · 2026Review
- The role of HMGA1 in genome stability: Implications in human cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Circular nucleic acids at the host-virus interface: from immune modulation to therapeutic innovation.Frontiers in immunology · 2026Review
- Predictive value of hepatic, hematological, and immunological markers and their temporal dynamics in chronic hepatitis B functional cure.Microbiology spectrum · 2025Article
- Homeobox protein MSX-1 restricts hepatitis B virus by promoting ubiquitin-independent proteasomal degradation of HBx protein.PLoS pathogens · 2025Article
- Identification and characterization of host factor VCPIP1 as a multi-functional positive regulator of hepatitis B virus.Journal of virology · 2024Article
- Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.Pathogens (Basel, Switzerland) · 2024Review
- HBx induces chemoresistance in diffuse large B cell lymphoma by inhibiting intrinsic apoptosis via the NF-κB/XIAP pathway.Molecular therapy. Nucleic acids · 2024Article
- The transcription factor HMGB2 indirectly regulates APRIL expression and Gd-IgA1 production in patients with IgA nephropathy.Renal failure · 2024Article
- [circ_0084043/miR-31-5p Is Involved in Atherosclerosis by Regulating HMGA1: Investigation of the Mechanisms].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- Epigenetics and environmental health.Frontiers of medicine · 2024Review
- HMGA1 promotes the progression of esophageal squamous cell carcinoma by elevating TKT-mediated upregulation of pentose phosphate pathway.Cell death & disease · 2024Article
- The RP11-417E7.1/THBS2 signaling pathway promotes colorectal cancer metastasis by activating the Wnt/β-catenin pathway and facilitating exosome-mediated M2 macrophage polarization.Journal of experimental & clinical cancer research : CR · 2024Article
- Intrahepatic homeobox protein MSX-1 is a novel host restriction factor of hepatitis B virus.Journal of virology · 2024Article
- From metabolism to malignancy: the multifaceted role of PGC1α in cancer.Frontiers in oncology · 2024Review
- Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.World journal of hepatology · 2023Review
- Herpes Simplex Virus 1 (HSV-1) Infected Cell Protein 0 (ICP0) Targets of Ubiquitination during Productive Infection of Primary Adult Sensory Neurons.International journal of molecular sciences · 2023Article
- Phosphorylation of UHRF2 affects malignant phenotypes of HCC and HBV replication by blocking DHX9 ubiquitylation.Cell death discovery · 2023Article
- Role of hepatitis B virus non-structural protein HBx on HBV replication, interferon signaling, and hepatocarcinogenesis.Frontiers in microbiology · 2023Review
- A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma.Frontiers in genetics · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic infection with hepatitis B virus (HBV) is associated with liver cirrhosis and hepatocellular carcinoma. Upon infection of hepatocytes, HBV covalently closed circular DNA (cccDNA) exists as histone-bound mini-chromosome, subjected to transcriptional regulation similar to chromosomal DNA. Here we identify high mobility group AT-hook 1 (HMGA1) protein as a positive regulator of HBV transcription that binds to a conserved ATTGG site within enhancer II/core promoter (EII/Cp) and recruits transcription factors FOXO3α and PGC1α. HMGA1-mediated upregulation of EII/Cp results in enhanced viral gene expression and genome replication. Notably, expression of endogenous HMGA1 was also demonstrated to be upregulated by HBV, which involves HBV X protein (HBx) interacting with SP1 transcription factor to activate HMGA1 promoter. Consistent with these in vitro results, chronic hepatitis B patients in immune tolerant phase display both higher intrahepatic HMGA1 protein levels and higher serum HBV markers compared to patients in inactive carrier phase. Finally, using a mouse model of HBV persistence, we show that targeting endogenous HMGA1 through RNA interference facilitated HBV clearance. These data establish HMGA1 as an important positive regulator of HBV that is reciprocally upregulated by HBV via HBx and also suggest the HMGA1-HBV positive feedback loop as a potential therapeutic target.
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