ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Lefamulin Overcomes Acquired Drug Resistance via Regulating Mitochondrial Homeostasis by Targeting ILF3 in Hepatocellular Carcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Pleuromutilins Suppress Hepatocellular Carcinoma Growth via ABCA1 Inhibition-Induced Cholesterol Accumulation.Cancers · 2026Article
- Performance of gradient diffusion strip and disk diffusion versus broth microdilution for lefamulin susceptibility testing of 422Journal of clinical microbiology · 2026Article
- Scaffolding of the H4K5ac chromatin remodeling complex by lncRNA MAHAC mediates epithelial-mesenchymal transition.Nucleic acids research · 2026Article
- Mitochondrial gatekeeper in hepatocellular carcinoma: Unraveling the multifaceted roles of VDAC in metabolic reprogramming, apoptosis evasion and therapeutic innovation (Review).Molecular medicine reports · 2026Review
- Lefamulin harbors promising anti-tuberculosis activity against multidrug-resistantMicrobiology spectrum · 2025Article
- Cardiomyocyte lncRNA Cpat maintains cardiac homeostasis and mitochondria function by targeting citrate synthase acetylation.Nature communications · 2025Article
- Oleanolic Acid Restores Drug Sensitivity in Sorafenib-resistant Hepatocellular Carcinoma: Evidence fromJournal of clinical and translational hepatology · 2025Article
- Simvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells.Cell death & disease · 2025Article
- [Research progress in the extent of hepatocellular carcinoma in the year 2024].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis.Hereditas · 2025Article
- Circular RNAs modulate cancer drug resistance: advances and challenges.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Lefamulin Overcomes Acquired Drug Resistance via Regulating Mitochondrial Homeostasis by Targeting ILF3 in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Acquired resistance represents a critical clinical challenge to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) treatment in hepatocellular carcinoma (HCC). Therefore, it is urgent to explore new mechanisms and therapeutics that can overcome or delay resistance. Here, a US Food and Drug Administration (FDA)-approved pleuromutilin antibiotic is identified that overcomes sorafenib resistance in HCC cell lines, cell line-derived xenograft (CDX) and hydrodynamic injection mouse models. It is demonstrated that lefamulin targets interleukin enhancer-binding factor 3 (ILF3) to increase the sorafenib susceptibility of HCC via impairing mitochondrial function. Mechanistically, lefamulin directly binds to the Alanine-99 site of ILF3 protein and interferes with acetyltransferase general control non-depressible 5 (GCN5) and CREB binding protein (CBP) mediated acetylation of Lysine-100 site, which disrupts the ILF3-mediated transcription of mitochondrial ribosomal protein L12 (MRPL12) and subsequent mitochondrial biogenesis. Clinical data further confirm that high ILF3 or MRPL12 expression is associated with poor survival and targeted therapy efficacy in HCC. Conclusively, this findings suggest that ILF3 is a potential therapeutic target for overcoming resistance to TKIs, and lefamulin may be a novel combination therapy strategy for HCC treatment with sorafenib and regorafenib.
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