ArticleOncogene2019
Sirtuin-mediated deacetylation of hnRNP A1 suppresses glycolysis and growth in hepatocellular carcinoma.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- The sirtuin family: from mechanisms to therapy.Molecular biomedicine · 2026Review
- CircRSU1 Activates the hnRNPA1/HIF-1α/CD24 Signaling Axis, Promoting Stemness Features of Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate-driven lactylation of HNRNPA1 orchestrates PKM2 splicing and glycolytic reprogramming in bladder cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
- PKM2-driven metabolic reprogramming in digestive system tumors: mechanisms, therapeutic advances, and clinical challenges.Frontiers in immunology · 2025Review
- Sirtuin 5 inhibits mitochondrial metabolism in liver cancer cells and promotes apoptosis by mediating the desuccinylation of CS.Frontiers in immunology · 2025Article
- The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.Molecular neurobiology · 2024Review
- Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions.Science advances · 2024Article
- The Regulatory Network of hnRNPs Underlying RegulatingBiomolecules · 2024Review
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS).Nature communications · 2024Article
- HNRNPA2B1 induces cell proliferation and acts as biomarker in breast cancer.Cancer biomarkers : section A of Disease markers · 2024Article
- Targeting the deacetylase SIRT6 unveils spliceosome deregulation as exploitable vulnerability for aggressive myeloma.Blood advances · 2023Article
- A comprehensive understanding of hnRNP A1 role in cancer: new perspectives on binding with noncoding RNA.Cancer gene therapy · 2023Review
- Review
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor cells undergo a metabolic shift in order to adapt to the altered microenvironment, although the underlying mechanisms have not been fully explored. HnRNP A1 is involved in the alternative splicing of the pyruvate kinase (PK) mRNA, allowing tumor cells to specifically produce the PKM2 isoform. We found that the acetylation status of hnRNP A1 in hepatocellular carcinoma (HCC) cells was dependent on glucose availability, which affected the PKM2-dependent glycolytic pathway. In the glucose-starved HCC cells, SIRT1 and SIRT6, members of deacetylase sirtuin family, were highly expressed and deacetylated hnRNP A1 after direct binding. We identified four lysine residues in hnRNP A1 that were deacetylated by SIRT1 and SIRT6, resulting in significant inhibition of glycolysis in HCC cells. Deacetylated hnRNP A1 reduced PKM2 and increased PKM1 alternative splicing in HCC cells under normal glucose conditions, thereby reducing the metabolic activity of PK and the non-metabolic PKM2-β-catenin signaling pathway. However, under glucose starvation, the low levels of acetylated hnRNP A1 reduced HCC cell metabolism to adapt to the nutrient deficiency. Taken together, sirtuin-mediated hnRNP A1 deacetylation inhibits HCC cell proliferation and tumorigenesis in a PKM2-dependent manner. These findings point to the metabolic reprogramming induced by hnRNP A1 acetylation in order to adapt to the nutritional status of the tumor microenvironment.
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Registered trials
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