ArticleBMC medicine2022
NUPR1 contributes to radiation resistance by maintaining ROS homeostasis via AhR/CYP signal axis in hepatocellular carcinoma.
Article in BMC medicine, 2022. 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, 39 citations in OpenAlex.
- METTL3 promotes proliferation and invasion and inhibits ferroptosis in hepatocellular carcinoma by mediating m6A methylation modification of NUPR1.Molecular and cellular biochemistry · 2026Article
- CRISPR/Cas9 screen identifies DCAF4 as a novel protector of hepatocellular carcinoma against brachytherapy via stress granule-dependent NRF2 activation.Cell death & disease · 2026Article
- NUPR1 as a central stress-adaptation node in cancer: integrating metabolic rewiring, cell death, and therapy resistance.Journal of biomedical science · 2026Review
- Endogenous Amplification of Apoptosis via p53 Regulation using a Cascade Nanocatalytic Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CS2164 combined with radiation suppressed tumor growth via γ-H2AX persistence and ROS accumulation.BMC cancer · 2026Article
- Spatiotemporal dynamics of reactive oxygen species: implications for cellular homeostasis and redox therapies.Cellular & molecular biology letters · 2026Review
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- NUPR1 in breast cancer: mechanisms and potential applications.Frontiers in physiology · 2026Review
- Hypoxic Reprogramming of ACOX1-Driven HSP90AB1 Crotonylation Stabilizes Thioredoxin to Orchestrate Redox Homeostasis in Oral Squamous Cell Carcinoma.Research (Washington, D.C.) · 2026Article
- Epithelial-Mesenchymal Transition and Stress Adaptations Underlie Yttrium-90 Resistance in Liver Cancer Cell Lines.Cancer research communications · 2026Article
- Aryl hydrocarbon receptor: a multifaceted environmental sensor in liver homeostasis and disease.Frontiers in medicine · 2026Review
- ACSS1 co-opts acetyl-CoA metabolism to drive DNA repair and undermine radiotherapy efficacy in breast cancer.Cell death & disease · 2025Article
- Article
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Disruption of glutamine transport uncouples the NUPR1 stress-adaptation program and induces prostate cancer radiosensitivity.Cell communication and signaling : CCS · 2025Article
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Lactylation-Driven NUPR1 Promotes Immunosuppression of Tumor-Infiltrating Macrophages in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Music therapy as a preventive intervention for postpartum depression: modulation of synaptic plasticity, oxidative stress, and inflammation in a mouse model.Translational psychiatry · 2025Article
- Integrin β6/Annexin A2 axis triggers autophagy to orchestrate hepatocellular carcinoma radioresistance.Cell death and differentiation · 2025Article
- Radioresistance in Hepatocellular Carcinoma: Biological Bases and Therapeutic Implications.International journal of molecular sciences · 2025Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRadiotherapy (RT) is one of the major therapeutic approaches to hepatocellular carcinoma (HCC). Ionizing radiation (IR) inducing the generation of reactive oxygen species (ROS) leads to a promising antitumor effect. However, the dysregulation of the redox system often causes radioresistance and impairs the efficacy of RT. Increasing evidence indicates that nuclear protein 1 (NUPR1) plays a critical role in redox reactions. In this study, we aim to explore the role of NUPR1 in maintaining ROS homeostasis and radioresistance in HCC.
methodsThe radioresistant role of NUPR1 was determined by colony formation assay, comet assay in vitro, and xenograft tumor models in vivo. Probes for ROS, apoptosis assay, and lipid peroxidation assay were used to investigate the functional effect of NUPR1 on ROS homeostasis and oxidative stress. RNA sequencing and co-immunoprecipitation assay were performed to clarify the mechanism of NUPR1 inhibiting the AhR/CYP signal axis. Finally, we analyzed clinical specimens to assess the predictive value of NUPR1 and AhR in the radiotherapeutic efficacy of HCC.
resultsWe demonstrated that NUPR1 was upregulated in HCC tissues and verified that NUPR1 increased the radioresistance of HCC in vitro and in vivo. NUPR1 alleviated the generation of ROS and suppressed oxidative stress, including apoptosis and lipid peroxidation by downregulating cytochrome P450 (CYP) upon IR. ROS scavenger N-acetyl-L-cysteine (NAC) and CYP inhibitor alizarin restored the viability of NUPR1-knockdown cells during IR. Mechanistically, the interaction between NUPR1 and aryl hydrocarbon receptor (AhR) promoted the degradation and decreased nuclear translation of AhR via the autophagy-lysosome pathway, followed by being incapable of CYP's transcription. Furthermore, genetically and pharmacologically activating AhR abrogated the radioresistant role of NUPR1. Clinical data suggested that NUPR1 and AhR could serve as novel biomarkers for predicting the radiation response of HCC.
conclusionsOur findings revealed the role of NUPR1 in regulating ROS homeostasis and oxidative stress via the AhR/CYP signal axis upon IR. Strategies targeting the NUPR1/AhR/CYP pathway may have important clinical applications for improving the radiotherapeutic efficacy of HCC.
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