ArticleOncogene2023
Hypoxia-responsive PPARGC1A/BAMBI/ACSL5 axis promotes progression and resistance to lenvatinib in hepatocellular carcinoma.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 88 citations in OpenAlex.
- Efficacy and safety of lenvatinib plus gefitinib in lenvatinib-resistant hepatocellular carcinomas: a prospective, single-arm exploratory trial.Signal transduction and targeted therapy · 2024Trial
- Coregulatory Networks Remodel the Disease-Specific Functions of Orphan Nuclear Receptor TR4.Cells · 2026Review
- Adipocyte-rich microenvironment promotes TNBC progression through SIRT6-associated ACSL5 dysregulation and lipid storage-associated phenotypes.Journal of experimental & clinical cancer research : CR · 2026Article
- Potential role of PPARGC1A in linking ulcerative colitis to colorectal cancer: a novel prognostic biomarker and therapeutic target.Translational cancer research · 2026Article
- Intracellular lipid droplets positively regulate the dormancy of colorectal cancer cells depending on ELF1-ACSL5 signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- miR-574-3p Regulates Smad/Snail Signaling to Promote Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma Cells.Biochemical genetics · 2026Article
- Integrative Transcriptomics and Machine Learning Reveal the Association of CBX4 with Inflammation in Ulcerative Colitis as a Potential Epigenetic Regulator.Biomedicines · 2026Article
- Deuterium modification of tyrosine kinase inhibitors contributes to reversing ferroptosis resistance through upregulation of aldehyde oxidase 1 in hepatocellular carcinoma.Acta pharmaceutica Sinica. B · 2026Article
- Gut-engineeredFrontiers in bioengineering and biotechnology · 2026Article
- Post-Translational Modification Networks in Ferroptosis: Orchestrating Defense, Drug Resistance, and Therapeutic Opportunities in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Single-Cell Transcriptomic Analysis Suggests That JUN May Regulate BAMBI to Promote Osteosarcoma Cell Migration and Invasion.Human mutation · 2026Article
- Mechanism and therapeutic prospects of ferroptosis regulation through m6A in cancer.Frontiers in cell and developmental biology · 2026Review
- Role and molecular mechanisms of hypoxia-derived exosomal miR-301a on gemcitabine resistance in pancreatic cancer.Oncology letters · 2025Article
- Hypoxia-mediated mJournal of translational medicine · 2025Review
- Roles of Hypoxia and Mitochondrial Energy Metabolism Related Genes in Predicting the Prognosis of Liver Hepatocellular Carcinoma.Digestive diseases and sciences · 2025Article
- EZH2 confers lenvatinib resistance in hepatocellular carcinoma by suppressing ACSL1-Mediated ferroptosis.BMC cancer · 2025Article
- miR-375 protects against acetaminophen-induced acute liver failure by orchestrating pharmacogene expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Exploring the role of ferroptosis in esophageal cancer: mechanisms and therapeutic implications.Cell death discovery · 2025Review
- Stemness-hypoxia genesTranslational cancer research · 2025Article
- Impact of altitude on hemoglobin dynamics and prognosis in patients with advanced hepatocellular carcinoma receiving antiangiogenic TKIs: A propensity score matched study.Cancer chemotherapy and pharmacology · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence has indicated that peroxisome proliferator-activated receptor-gamma coactivator-1α (PPARGC1A) is involved in hepatocellular carcinoma (HCC). However, its detailed function and up- and downstream mechanisms are incompletely understood. In this study, we confirmed that PPAGC1A is lowly expressed in HCC and is associated with poor prognosis using large-scale public datasets and in-house cohorts. PPAGC1A was found to impair the progression and sensitivity of HCC to lenvatinib. Mechanistically, PPAGC1A repressed bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) by inhibiting WNT/β-catenin signaling. BAMBI mediated the function of PPARGC1A and regulated ACSL5 through TGF-β/SMAD signaling. PPARGC1A/BAMBI regulated ROS production and ferroptosis-related cell death by controlling ACSL5. PPARGC1A/BAMBI/ACSL5 axis was hypoxia-responsive. METTL3 and WTAP silenced PPARGC1A in an m6A-YTHDF2-dependent way under normoxia and hypoxia, respectively. Metformin restored PPARGC1A expression by reducing its m6A modification via inhibiting METTL3. In animal models and patient-derived organoids, consistent functional data of PPARGC1A/BAMBI/ACSL5 were observed. Conclusions: These findings provide new insights into the role of the aberrant PPARGC1A/BAMBI/ACSL5 axis in HCC. And the mechanism of PPARGC1A dysregulation was explained by m6A modification. Metformin may benefit HCC patients with PPARGC1A dysregulation.
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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 Socratic graph.