ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Lactate Metabolic Reprogramming Mediated by CircRNA-LDHA Complex Facilitates Innate Immune Evasion of Liver Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Comparative efficacy and safety of first-line treatments for advanced hepatocellular carcinoma: a Bayesian network meta-analysis.Frontiers in immunology · 2026Pooled it
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Ginsenosides: potential therapeutic agents against hepatic fibrosis.Journal of ginseng research · 2026Review
- Metabolic Regulation of Immune Responses: Molecular Mechanisms, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- CircRNAs in Immuno-Metabolic Reprogramming of Chordoma Cancer: Molecular Crosstalk and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Metabolic immune checkpoints in cancer: how tumor-derived metabolites shape immunotherapy resistance.Frontiers in immunology · 2026Review
- Shikonin in Hepatocellular Carcinoma: Bridging Metabolic Disruption and Immunomodulation.Journal of hepatocellular carcinoma · 2026Review
- Hub circRNAs in cancer: dual regulation of metastasis and immune evasion.Frontiers in immunology · 2026Review
- Functional roles and mechanisms of circRNA-protein interactions in cancer progression and tumor immune regulation.Frontiers in immunology · 2026Review
- Lactate Metabolic Reprogramming Mediated by CircRNA-LDHA Complex Facilitates Innate Immune Evasion of Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) exhibits a distinctive metabolic profile that engenders a highly immunosuppressive tumor immune microenvironment, posing significant challenges for targeted therapy. Notably, natural killer (NK) cells, which are abundant in the liver and play a crucial role in innate immunity, are attracting growing attention in HCC immunotherapy. Previously, circular RNAs (circRNAs) have emerged as significant regulators in tumor development. Here, an in vitro NK-cell-driven tumor evolution model is innovatively established and a novel circRNA, circSMPD4 is identified, which induces lactate metabolic reprogramming in tumor, ultimately promoting immune evasion and metastasis. Lactate dehydrogenase A (LDHA), a main subunit of the critical enzyme in lactate metabolism, is identified as the core effector of circSMPD4's biological function. Mechanistically, circSMPD4 physically combines LDHA to reduce its acetylation levels via SIRT2-dependent deacetylation and thus preventing its degradation from chaperone-mediated autophagy-lysosome pathway. These findings unveil an oncogenic circRNA and elucidate a novel regulatory mechanism by which tumor cell metabolic reprogramming facilitates tumor immune evasion and tumor progression.
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Registered trials
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