ArticleCancer biology & therapy2017
CRISPR/Cas9-based Pten knock-out and Sleeping Beauty Transposon-mediated Nras knock-in induces hepatocellular carcinoma and hepatic lipid accumulation in mice.
Article in Cancer biology & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 30 citations in OpenAlex.
- Transcriptional regulation of ubiquitin specific peptidase 2b by farnesoid X receptor and its implications in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2026Article
- Perilipin 2 Mediates Progression of Lung Adenocarcinoma by Modulating Lipid Metabolism.The American journal of pathology · 2025Article
- Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.Clinical science (London, England : 1979) · 2024Article
- A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma.Oncology research · 2024Review
- USP35 promotes HCC development by stabilizing ABHD17C and activating the PI3K/AKT signaling pathway.Cell death discovery · 2023Article
- High-expressed PTPN1 promotes tumor proliferation signature in human hepatocellular carcinoma.Heliyon · 2023Article
- Hydrodynamic Delivery: Characteristics, Applications, and Technological Advances.Pharmaceutics · 2023Review
- Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing.Molecular medicine reports · 2022Article
- The power and the promise of CRISPR/Cas9 genome editing for clinical application with gene therapy.Journal of advanced research · 2022Review
- Insertion Specificity of the hATx-6 Transposase ofFrontiers in molecular biosciences · 2021Article
- Biogenesis and Breakdown of Lipid Droplets in Pathological Conditions.Frontiers in cell and developmental biology · 2021Review
- Identification and analysis of circRNA-miRNA-mRNA regulatory network in hepatocellular carcinoma.IET systems biology · 2020Article
- Review
- Diet induces hepatocyte protection in fatty liver disease via modulation of PTEN signaling.Biomedical reports · 2020Article
- Lipid droplet and its implication in cancer progression.American journal of cancer research · 2020Review
- Using CRISPR/Cas9 to model human liver disease.JHEP reports : innovation in hepatology · 2019Review
- Review
- Overexpression of HGF/MET axis along with p53 inhibition induces de novo glioma formation in mice.Neuro-oncology advancesArticle
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten and overexpression of Nras were achieved in out-bred immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated Pten knockout system. Concurrent Pten knockout and Nras knock-in induced hepatocellular carcinoma, while individual gene manipulation failed. Tumor development was associated with liver fibrosis, hyperlipidemia, hepatic deposition of lipid droplets and glycogen, and hepatomegaly. At the molecular level, lipid droplet formation was primarily contributed by upregulated expression of genes responsible for lipogenesis and fatty acid sequestration, such as Srebpf1, Acc, Pparg and its downstream targets. Our findings demonstrated that Pten disruption was synergized by Nras overexpression in driving hepatocyte malignant transformation, which correlated with extensive formation of lipid droplets.
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