ArticleOncogene2020
Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- The mitochondria enzyme OGDH defends against disulfidptosis by licensing METTL3-regulated NRF2 translation.Nature cell biology · 2026Article
- Functional roles and clinical implications of pseudogenes signatures as emerging biomarkers in cancer.Discover oncology · 2026Review
- Nur77 agonism invigorates Natural Killer cell immunity against hepatocellular carcinoma.Nature communications · 2026Article
- WFDC21P is essential for G3BP1-mediated RIG-I activation and antitumor immunity in triple-negative breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The ANXA2P1-hnRNP F-HK2/c-Myc Positive Feedback Loop Promotes Proliferation and Glycolytic Metabolism in Gastric Cancer.International journal of biological sciences · 2026Article
- NR4A1 Regulates Glycolysis in M1 Macrophages via the Wnt/β-Catenin Pathway to Affect Sepsis-Induced Myocardial Injury.Journal of inflammation research · 2026Article
- CENTRA: knowledge-based gene contextuality graphs reveal functional master regulators by centrality and fractality.NAR genomics and bioinformatics · 2025Article
- Phosphofructokinase-1 redefined: a metabolic hub orchestrating cancer hallmarks through multi-dimensional control networks.Journal of translational medicine · 2025Review
- Long noncoding RNAs regulating enzymatic reactions in cancer.Experimental & molecular medicine · 2025Review
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Emerging Roles of ncRNAs Regulating PKM2 in Cancer Progression.Current pharmaceutical biotechnology · 2025Review
- Discovery of a novel exceptionally potent and orally active Nur77 ligand NB1 with a distinct binding mode for cancer therapy.Acta pharmaceutica Sinica. B · 2024Article
- LncRNA NORFA promotes the synthesis of estradiol and inhibits the apoptosis of sow ovarian granulosa cells through SF-1/CYP11A1 axis.Biology direct · 2024Article
- Deciphering the nexus between long non-coding RNAs and endoplasmic reticulum stress in hepatocellular carcinoma: biomarker discovery and therapeutic horizons.Cell death discovery · 2024Review
- Nur77 protects the bladder urothelium from intracellular bacterial infection.Nature communications · 2024Article
- Activation of the G Protein-Coupled Bile Acid Receptor TGR5 Modulates the HCP5/miR-139-5p/DDIT4 Axis to Antagonize Cervical Cancer Progression.International journal of molecular sciences · 2024Article
- Involvement of lncRNAs in the regulation of aerobic glycolysis in hepatocellular carcinoma: Main functions, regulatory mechanisms and potential therapeutic implications (Review).Oncology reports · 2024Review
- Nur77-IRF1 axis inhibits esophageal squamous cell carcinoma growth and improves anti-PD-1 treatment efficacy.Cell death discovery · 2024Article
- LncRNA WFDC21P interacts with SEC63 to promote gastric cancer malignant behaviors by regulating calcium homeostasis signaling pathway.Cancer cell international · 2024Article
- Role of long non-coding RNAs in metabolic reprogramming of gastrointestinal cancer cells.Cancer cell international · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Orphan nuclear receptor Nur77, which is low expressed in HCC, functions as a tumor suppressor to suppress HCC. However, the detailed mechanism is still not well understood. Here, we demonstrate that Nur77 could inhibit HCC development via transcriptional activation of the lncRNA WAP four-disulfide core domain 21 pseudogene (WFDC21P). Nur77 binds to its response elements on the WFDC21P promoter to directly induce WFDC21P transcription, which inhibits HCC cell proliferation, tumor growth, and tumor metastasis both in vitro and in vivo. In clinical HCC samples, WFDC21P expression positively correlated with that of Nur77, and the loss of WFDC21P is associated with worse prognosis. Mechanistically, WFDC21P could inhibit glycolysis by simultaneously interacting with PFKP and PKM2, two key enzymes in glycolysis. These interactions not only abrogate the tetramer formation of PFKP to impede its catalytic activity but also prevent the nuclear translocation of PKM2 to suppress its function as a transcriptional coactivator. Cytosporone-B (Csn-B), an agonist for Nur77, could stimulate WFDC21P expression and suppress HCC in a WFDC21P-dependent manner. Therefore, our study reveals a new HCC suppressor and connects the glycolytic remodeling of HCC with the Nur77-WFDC21P-PFKP/PKM2 axis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.