ArticleBritish journal of cancer2011
Hepatitis B virus X protein downregulates expression of the miR-16 family in malignant hepatocytes in vitro.
Article in British journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 89 citations in OpenAlex.
- Viral-Track integrated single-cell RNA-sequencing reveals HBV lymphotropism and immunosuppressive microenvironment in HBV-associated hepatocellular carcinoma.Communications biology · 2025Article
- Plasma microRNA-15a/16-1 serves as a non-invasive indicator of liver fibrosis severity in individuals with chronic hepatitis B.Non-coding RNA research · 2024Article
- Plasma microRNA-15a/16-1-based machine learning for early detection of hepatitis B virus-related hepatocellular carcinoma.Liver research (Beijing, China) · 2024Article
- MicroRNAs participate in the regulation of apoptosis and oxidative stress-related gene expression in rabbits infected withFrontiers in microbiology · 2024Article
- Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Micro-Players of Great Significance-Host microRNA Signature in Viral Infections in Humans and Animals.International journal of molecular sciences · 2022Review
- Nonsynonymous C1653T Mutation of Hepatitis B Virus X Gene Enhances Malignancy of Hepatocellular Carcinoma Cells.Journal of hepatocellular carcinoma · 2022Article
- Crosstalk between Environmental Inflammatory Stimuli and Non-Coding RNA in Cancer Occurrence and Development.Cancers · 2021Review
- Cell death pathways and viruses: Role of microRNAs.Molecular therapy. Nucleic acids · 2021Review
- Advances on molecular mechanism of hepatitis B virus-induced hepatocellular carcinoma.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- Review
- Association of LIN28B polymorphisms with chronic hepatitis B virus infection.Virology journal · 2020Article
- Exosomal miRNAs in hepatitis B virus related liver disease: a new hope for biomarker.Gut pathogens · 2020Review
- Review
- Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications.Nature reviews. Gastroenterology & hepatology · 2018Review
- Inhibition of HBV replication by delivering the dual-gene expression vector pHsa-miR16-siRNA in HepG2.2.15 cells.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2017Article
- MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection.Oncology letters · 2017Article
- Hepatitis B virus X protein-mediated non-coding RNA aberrations in the development of human hepatocellular carcinoma.Experimental & molecular medicine · 2017Review
- HBx promotes cell proliferation by disturbing the cross-talk between miR-181a and PTEN.Scientific reports · 2017Article
- The role of microRNAs in hepatocyte metabolism and hepatitis B virus replication.Virologica Sinica · 2016Review
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
backgroundHepatitis B virus X protein (HBx) is involved in the initiation and progression of hepatocellular carcinoma (HCC) by regulating the host protein-coding genes. In this study, we showed that HBx altered the expression of microRNAs (miRNAs) to promote proliferation and transformation in malignant hepatocytes in vitro.
methodsmiRNA microarray and quantitative reverse-transcription polymerase chain reactions (qRT-PCRs) were performed to identify miRNAs that were differentially regulated by HBx in HCC cells. Protein, mRNA, and miRNA expression analyses; cell cycle and apoptosis analyses; loss/gain-of-function analysis; and luciferase reporter assays were performed to delineate the consequences of miR-16 family repression in HepG2 cells.
resultsHepatitis B virus X protein induced widespread deregulation of miRNAs in HepG2 cells, and the downregulation of the miR-16 family was reproducible in HepG2, SK-HEP-1, and Huh7 cells. CCND1, a target of the miR-16 family, was derepressed by HBx in HepG2 cells. c-Myc mediated the HBx-induced repression of miR-15a/16 in HepG2 cells. Ectopically expressed miR-15a/16 suppressed the proliferation, clonogenicity, and anchorage-independent growth of HBx-expressing HepG2 cells by arresting them in the G1 phase and inducing apoptosis, whereas reduced expression of miR-16 accelerated the growth and cell-cycle progression of HepG2 cells.
conclusionsHepatitis B virus X protein altered the in vitro expression of miRNAs in host malignant hepatocytes, particularly downregulating the miR-16 family. Repression of miR-15a/16 is c-Myc mediated and is required for the HBx-induced transformation of HepG2 cells in vitro. Therefore, miR-16 family may serve as a therapeutic target for hepatitis B virus (HBV)-associated HCC.
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