ArticleCell death & disease2021
RPRD1A stabilizes NRF2 and aggravates HCC progression through competing with p62 for TRIM21 binding.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Extracellular vesicle-mediated GALNT1/RPRD1A glycosylation axis drives immune escape and peritoneal metastasis in gastric cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Opposing Roles of CREPT and p15RS in Tumorigenesis via Differential Regulation of Wnt Signaling.Cancers · 2026Article
- RPRD1A drives lenvatinib resistance in hepatocellular carcinoma via the ITGA5-FAK signaling axis.Molecular biomedicine · 2026Article
- TRIM21 as a Context-Dependent Regulator in Hepatocellular Carcinoma: Integrating Etiological Landscapes (HBV/NASH) with Core Tumor Progression Mechanisms.Journal of hepatocellular carcinoma · 2026Review
- The NRF2 signaling pathway in hepatocellular carcinoma: dual roles, epigenetic reprogramming, and therapeutic opportunities in metabolic vulnerability.Frontiers in oncology · 2026Review
- Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4-β-catenin complex and downregulation of SOX9.Communications biology · 2024Article
- Autoantibody repertoire profiling in tissue and blood identifies colorectal cancer-specific biomarkers.Cancer science · 2024Article
- Intricate confrontation: Research progress and application potential of TRIM family proteins in tumor immune escape.Journal of advanced research · 2023Review
- The interconnected roles of TRIM21/Ro52 in systemic lupus erythematosus, primary Sjögren's syndrome, cancers, and cancer metabolism.Cancer cell international · 2023Review
- Battles against aberrant KEAP1-NRF2 signaling in lung cancer: intertwined metabolic and immune networks.Theranostics · 2023Review
- TRIM family contribute to tumorigenesis, cancer development, and drug resistance.Experimental hematology & oncology · 2022Review
- The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment.Frontiers in immunology · 2022Review
- The prognostic value and clinical significance of mitophagy-related genes in hepatocellular carcinoma.Frontiers in genetics · 2022Article
Corrections and comments
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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
NRF2 is the master transcriptional activator of cytoprotective genes and Kelch-like ECH-associated protein 1 (Keap1), a biosensor for electrophiles and oxidation, promotes NRF2 degradation in unstressed conditions. SQSTM1/p62, an oncogenic protein aberrantly accumulated in hepatocellular carcinoma (HCC), binds and sequestrates Keap1, leading to the prevention of NRF2 degradation. Here, we show that p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A) is highly expressed in HCC tumors and correlated with aggressive clinicopathological features. RPRD1A competitively interacts with TRIM21, an E3 ubiquitin ligase of p62, resulting in the decrease of p62 ubiquitination and the increased sequestration for Keap1. Therefore, RPRD1A enhances the nuclear translocation of NRF2, which induces gene expression for counteracting oxidative stress, maintaining cancer cells survival, and promoting HCC development. Moreover, disturbing the redox homeostasis of cancer cells by genetic knockdown of RPRD1A sensitizes cancer cells to platinum-induced cell death. Our study reveals RPRD1A is involved in the oxidative stress defense program and highlights the therapeutic benefits of targeting pathways that support antioxidation.
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