ArticleCell communication and signaling : CCS2019
NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Glycolytic reprogramming and the EMT drive cervical cancer progression via the NQO1/HIF1α-SIX1 axis.iScience · 2026Article
- Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA-NQO1/PP2A Switch to Activate PP2A.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sulforaphane-Activated Functional Nucleic Acids for Cancer Therapy: Mechanisms, Delivery Strategies, and Nanomedicine Advances.International journal of molecular sciences · 2026Review
- X-Linked Inhibitor of Apoptosis Protein (XIAP) Contributes to ERK1/2-Mediated Anoikis Resistance in Hepatocellular Carcinoma.MedComm - Oncology · 2026Article
- Tryptophan-EnrichedBiomaterials research · 2026Article
- Targeting MED23 inhibits hepatocellular carcinoma development by suppressing compensatory proliferation and facilitating ROS-mediated cell death.Cell death & disease · 2025Article
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Article
- Bioinformatics and machine learning driven key genes screening for hepatocellular carcinoma.Biochemistry and biophysics reports · 2024Article
- NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma.Current medical science · 2024Article
- Impact of NQO1 dysregulation in CNS disorders.Journal of translational medicine · 2024Review
- Cartilage-specificAnnals of the rheumatic diseases · 2023Article
- NQO1 drives glioblastoma cell aggressiveness through EMT induction via the PI3K/Akt/mTOR/Snail pathway.International journal of oncology · 2023Article
- Sirtuins at the Crossroads between Mitochondrial Quality Control and Neurodegenerative Diseases: Structure, Regulation, Modifications, and Modulators.Aging and disease · 2023Review
- The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis.International journal of molecular sciences · 2023Review
- Integrated analysis of ferroptosis-related gene signature for overall survival prediction in Asian patients with hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Review
- TCMSID: a simplified integrated database for drug discovery from traditional chinese medicine.Journal of cheminformatics · 2022Article
- SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.Aging and disease · 2022Review
- The caspase-2 substrate p54nrb exhibits a multifaceted role in tumor cell death susceptibility via gene regulatory functions.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOur previous study has demonstrated that NAD(P)H: quinone oxidoreductase 1 (NQO1) is significantly upregulated in human liver cancer where it potentiates the apoptosis evasion of liver cancer cell. However, the underlying mechanisms of the oncogenic function of NQO1 in HCC have not been fully elucidated.
methodsExpression of NQO1, SIRT6, AKT and X-linked inhibitor of apoptosis protein (XIAP) protein were measured by western blotting and immunohistochemistry. Additionally, the interaction between NQO1 and potential proteins were determined by immunoprecipitation assays. Furthermore, the effect of NQO1 and SIRT6 on tumor growth was determined in cell model and orthotopic tumor implantation model.
resultsWe found that NQO1 overexpression in HCC enhanced SIRT6 protein stability via inhibiting ubiquitin-mediated 26S proteasome degradation. High level of SIRT6 reduced acetylation of AKT which resulted in increased phosphorylation and activity of AKT. Activated AKT subsequently phosphorylated anti-apoptotic protein XIAP at Ser87 which determined its protein stability. Reintroduction of SIRT6 or AKT efficiently rescued NQO1 knock-out-mediated inhibition of growth and induction of apoptosis. In orthotopic mouse model, NQO1 knock-out inhibited tumor growth and induced apoptosis while this effect was effectively rescued by SIRT6 overexpression or MG132 treatment partially.
conclusionsCollectively, these results reveal an oncogenic function of NQO1 in sustaining HCC cell proliferation through SIRT6/AKT/XIAP signaling pathway.
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