ArticleCancer medicine2019
SIRT3 elicited an anti-Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic networks to breast cancer survival.GeroScience · 2026Article
- Mitochondrial PDHA1 acetylation orchestrates lactate-dependent epigenetic reprogramming to promote fibrosis via NUAK2.Cellular and molecular life sciences : CMLS · 2026Article
- SIRT3 suppresses renal cancer progression by regulating IDH2 acetylation.Scientific reports · 2026Article
- Beyond the convergence of metabolic reprogramming in primary liver cancer: a comprehensive review on energy and lipids metabolism.Frontiers in cell and developmental biology · 2026Review
- PGC-1α: a potential therapeutic target for upper airway dilator muscle structure and dysfunction in OSA.Sleep & breathing = Schlaf & Atmung · 2025Review
- Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance.Frontiers in immunology · 2025Review
- Roles of SIRT3 in aging and aging-related diseases.International journal of biological sciences · 2025Review
- Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.Cancers · 2024Review
- Protein regulator of cytokinesis 1 accentuates cholangiocarcinoma progression via mTORC1-mediated glycolysis.Human cell · 2024Article
- Targeting Glycolytic Reprogramming in Cholangiocarcinoma: A Novel Approach for Metabolic Therapy.Journal of inflammation research · 2024Review
- The role of metabolic reprogramming in liver cancer and its clinical perspectives.Frontiers in oncology · 2024Review
- The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- Identification of the function ofTranslational cancer research · 2023Article
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
- Circ_0000284 facilitates the growth, metastasis and glycolysis of intrahepatic cholangiocarcinoma through miR-152-3p-mediated PDK1 expression.Histology and histopathology · 2023Article
- PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response.Antioxidants (Basel, Switzerland) · 2023Review
- Impairment of electron transport chain and induction of apoptosis by chrysin nanoparticles targeting succinate-ubiquinone oxidoreductase in pancreatic and lung cancer cells.Genes & nutrition · 2023Article
- Metabolic reprogramming induced by DCA enhances cisplatin sensitivity through increasing mitochondrial oxidative stress in cholangiocarcinoma.Frontiers in pharmacology · 2023Article
- ISGylation of EMD promotes its interaction with PDHA to inhibit aerobic oxidation in lung adenocarcinoma.Journal of cellular and molecular medicine · 2022Article
- The Role of SIRT3 in Exercise and Aging.Cells · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholangiocarcinoma (CCA) is an extremely invasive malignancy with late diagnosis and unfavorable prognosis. Surgery and chemotherapy are still not effective in improving outcomes in CCA patients. It is crucial to explore a novel therapeutic target for treating CCA. An NAD-dependent deacetylase also known as Sirtuin-3 (SIRT3) has been shown to regulate cellular metabolism in various cancers dynamically. However, the biological function of SIRT3 in CCA remains unclear. In this study, bioinformatics analyses were performed to identify the differentially expressed genes and pathways enriched. CCA samples were collected for immunohistochemical analysis. Three human CCA cell lines (HuCCT1, RBE, and HCCC9810) were used to explore the molecular mechanism of SIRT3 regulation of metabolic reprogramming and malignant behavior in CCA. A CCA xenograft model was then established for further validation in vivo. The data showed that SIRT3 expression was decreased and glycolysis was enhanced in CCA. Similar metabolic reprogramming was also observed in SIRT3 knockout mice. Furthermore, we demonstrated that SIRT3 could play an anti-Warburg effect by inhibiting the hypoxia-inducible factor-1α (HIF1α)/pyruvate dehydrogenase kinase 1 (PDK1)/pyruvate dehydrogenase (PDHA1) pathway in CCA cells. CCA cell proliferation and apoptosis were regulated by SIRT3-mediated metabolic reprogramming. These findings were further confirmed in CCA clinical samples and the xenograft model. Collectively, this study suggests that in the inhibition of CCA progression, SIRT3 acts through an anti-Warburg effect on the downstream pathway HIF1α/PDK1/PDHA1.
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