ArticleJournal of cellular and molecular medicine2019
ISG12a and its interaction partner NR4A1 are involved in TRAIL-induced apoptosis in hepatoma cells.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 15 citations in OpenAlex.
- Mitochondria as the Hub of Apoptosis: A Comprehensive Insight From Mitochondria to Interactions With Other Organelles.MedComm · 2026Review
- The IFN-induced protein IFI27 binds MDA5 and counteracts its activation after SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2024Article
- Carboxypeptidase A4 negatively regulates HGS-ETR1/2-induced pyroptosis by forming a positive feedback loop with the AKT signalling pathway.Cell death & disease · 2023Article
- Overexpression of RBM34 Promotes Tumor Progression and Correlates with Poor Prognosis of Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Article
- The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling.Frontiers in microbiology · 2023Article
- The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.International journal of molecular sciences · 2022Article
- SNRPB is a mediator for cellular response to cisplatin in non-small-cell lung cancer.Medical oncology (Northwood, London, England) · 2021Article
- The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.Molecular cancer research : MCR · 2021Review
- Mechanical Stretching induces the apoptosis of parametrial ligament Fibroblasts via the Actin Cytoskeleton/Nr4a1 signalling pathway.International journal of medical sciences · 2020Article
- ISG12a and its interaction partner NR4A1 are involved in TRAIL-induced apoptosis in hepatoma cells.Journal of cellular and molecular medicine · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells while sparing normal cells, thereby leading to the development of TRAIL receptor agonists for cancer treatment. However, these agonist-based therapeutics exhibit little clinical benefits due to the lack of biomarkers to predict whether patients are responsive to the treatment, as well as determine the resistance of cancer cells to TRAIL-based agonists. Our previous study has demonstrated that ISG12a enhances TRAIL-induced apoptosis and might serve as a biomarker to predict the TRAIL response. The downstream mechanism by which ISG12a augments TRAIL-induced apoptosis remains to be elucidated. In this study, we found that ISG12a was localized in the mitochondria and nucleus and augmented TRAIL-induced apoptosis through intrinsic apoptotic pathway. In addition, ISG12a interacted with NR4A1 and promoted its nuclear-to-cytoplasm translocation. Upon translocate to cytoplasm, NR4A1 targeted mitochondria and induced Bcl2 conformational change, thereby exposing its BH3 domain. Moreover, TRAIL treatment can induce NR4A1 expression through the activation of NF-κB in TRAIL-resistant Huh7 hepatoma cells. Knockdown of NR4A1 could overcome TRAIL resistance. However, in TRAIL-sensitive LH86 liver cancer cells, TRAIL activated the Jun N-terminal kinases signalling pathway. Overall, these results showed that both ISG12a and its interaction partner NR4A1 are involved in TRAIL-mediated apoptosis in hepatoma cells.
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