ArticleNeoplasia (New York, N.Y.)2019
Neuroblastoma RAS Viral Oncogene Homolog (NRAS) Is a Novel Prognostic Marker and Contributes to Sorafenib Resistance in Hepatocellular Carcinoma.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Novel function of GTPBP2 in promoting hepatocellular carcinoma progression through inhibition of BTRC-mediated KRAS degradation.Cancer cell international · 2026Article
- Assessment of Circulating Tumor DNA for Early Detection of Hepatocellular Carcinoma in Alpha-Fetoprotein-Negative Patients With Cirrhotic Nodules.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Article
- A prognostic model of 8-T/B cell receptor-related signatures for hepatocellular carcinoma.Discover oncology · 2025Article
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- Advancements in leukemia management: Bridging diagnosis, prognosis and nanotechnology (Review).International journal of oncology · 2024Review
- Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.Nature communications · 2024Article
- Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.Nature communications · 2024Article
- Establishment and verification of a prognostic risk score model based on immune genes for hepatocellular carcinoma in an Asian population.Translational cancer research · 2023Article
- Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis.Cell death & disease · 2023Article
- Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases.Translational cancer research · 2023Article
- Establishment and validation of a ferroptosis-related prognostic signature for hepatocellular carcinoma.Frontiers in oncology · 2023Article
- Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach.Journal of microbiology and biotechnology · 2022Article
- NRAS expression is associated with prognosis and tumor immune microenvironment in lung adenocarcinoma.Journal of cancer research and clinical oncology · 2022Article
- Prognostic model of immune-related genes for patients with hepatocellular carcinoma.Frontiers in surgery · 2022Article
- Ferroptosis-Related Hub Genes in Hepatocellular Carcinoma: Prognostic Signature, Immune-Related, and Drug Resistance Analysis.Frontiers in genetics · 2022Article
- Comprehensive analysis of the cancer driver genes constructs a seven-gene signature for prediction of survival and tumor immunity in hepatocellular carcinoma.Frontiers in genetics · 2022Article
- A novel immune-related gene signature predicts the prognosis of hepatocellular carcinoma.Frontiers in oncology · 2022Article
- Serial circulating tumor DNA to predict early recurrence in patients with hepatocellular carcinoma: a prospective study.Molecular oncology · 2022Article
- microRNA-181a-5p impedes the proliferation, migration, and invasion of retinoblastoma cells by targeting the NRAS proto-oncogene.Clinics (Sao Paulo, Brazil) · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of the RAS-RAF-ERK-pathway using sorafenib as a first-line and regorafenib as a second-line treatment approach is the only effective therapeutic strategy for advanced hepatocellular carcinoma (HCC). Recent studies suggest that wild-type KRAS and HRAS isoforms could majorly contribute to HCC progression and sorafenib resistance. In contrast, the role of neuroblastoma RAS viral oncogene homolog (NRAS) in HCC remained elusive. In this study, wild-type NRAS was found to be overexpressed in HCC cell lines, preclinical HCC models, and human HCC tissues. Moreover, NRAS overexpression correlated with poor survival and proliferation in vivo. However, si-RNA-pool-mediated NRAS knockdown showed only slight effects on HCC proliferation, clonogenicity, and AKT activity. We determined that KRAS upregulation served as a functional compensatory mechanism in the absence of NRAS, which was overcome by combined inhibition of NRAS and KRAS in HCC cells. Furthermore, NRAS expression was elevated in sorafenib-resistant compared to nonresistant HCC cells, and NRAS knockdown enhanced sorafenib efficacy in resistant cells. In summary, NRAS appears to be a prognostic marker in HCC and contributes to sorafenib resistance. Regarding potential therapeutic strategies, NRAS inhibition in HCC should be combined with KRAS inhibition to prevent KRAS-mediated rescue effects.
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