ArticleJournal of hepatology2023
Decreased propionyl-CoA metabolism facilitates metabolic reprogramming and promotes hepatocellular carcinoma.
Article in Journal of hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Metabolic reprogramming in hepatocellular carcinoma: a bibliometric and visualized study from 2011 to 2023.Frontiers in pharmacology · 2024Pooled it
- Propionyl-CoA catabolism is a metabolic gatekeeper for fatty acid oxidation in pancreatic cancer.Oncogene · 2026Article
- Article
- Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism.Nature metabolism · 2026Article
- Tissue Heterogeneity-Driven Parallel Acquisition for High-Coverage MS/MS Imaging of Lipids.Angewandte Chemie (International ed. in English) · 2026Article
- Reprogramming of valine metabolism mediated by abnormally low ALDH6A1 expression promotes invasive metastasis of gastric cancer.Science advances · 2026Article
- PDIA6 exacerbates hepatocellular carcinoma via enhancing proteasome-dependent degradation of AKAP12.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- ENO1 interacts with PKM to promote HBV-related hepatocellular carcinoma progression and HBV replication.Journal of translational medicine · 2026Article
- Lysine Propionylation as a Metabolically Coupled PTM: Mechanisms, Functional Consequences, and Therapeutic Potentials.International journal of molecular sciences · 2026Review
- Construction of a survival model for predicting biochemical recurrence of prostate cancer based on propionate metabolism-related genes.Translational andrology and urology · 2026Article
- Integrated multi-omics analysis reveals comprehensive metabolism-driven tumor heterogeneity and immune microenvironment in hepatocellular carcinomas.Scientific reports · 2026Article
- ALDH2 inhibits head and neck tumorigenesis through RAS signaling suppression, transactivation of TGM2, and synergy with ALDH6A1.Cellular and molecular life sciences : CMLS · 2026Article
- Tenuigenin regulates succinylation via SIRT5 for suppressing the tumorigenicity of hepatocellular carcinoma cells.Frontiers in pharmacology · 2026Article
- Integrated Bioinformatics Analysis Revealing that the NSDHL Gene Might Be Associated with the Progression of Western HFD/SW-Induced Hepatocellular CarcinomaEndocrine, metabolic & immune disorders drug targets · 2026Article
- The novel circular RNA circG6pc attenuates oxidative stress and mitochondrial damage through miR-7018-5p/Aldh6a1 axis in kidney fibrosis.Cellular & molecular biology letters · 2025Article
- Post-translational acylation of proteins in cardiac hypertrophy.Nature reviews. Cardiology · 2025Review
- A constraint-based framework for exploring the impact of multireaction dependencies on metabolic functions.NPJ systems biology and applications · 2025Article
- Liver-specific propanoate metabolism-derived 2-ethylhexanol as a novel biomarker for precise diagnosis and prognosis of hepatocellular carcinoma.Biomarker research · 2025Article
- Pak4-mediated crosstalk between necroptotic macrophages and tendon stem/progenitor cells contributes to traumatic heterotopic ossification formation.Bone research · 2025Article
- Integrating bulk RNA-seq, scRNA-seq, and spatial transcriptomics data to identify novel post-translational modification-related molecular subtypes and therapeutic responses in hepatocellular carcinoma.Cancer cell international · 2025Article
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsAlterations of multiple metabolites characterize distinct features of metabolic reprograming in hepatocellular carcinoma (HCC). However, the role of most metabolites, including propionyl-CoA (Pro-CoA), in metabolic reprogramming and hepatocarcinogenesis remains elusive. In this study, we aimed to dissect how Pro-CoA metabolism affects these processes.
methodsTCGA data and HCC samples were used to analyze ALDH6A1-mediated Pro-CoA metabolism and its correlation with HCC. Multiple metabolites were assayed by targeted mass spectrometry. The role of ALDH6A1-generated Pro-CoA in HCC was evaluated in HCC cell lines as well as xenograft nude mouse models and primary liver cancer mouse models. Non-targeted metabolomic and targeted energy metabolomic analyses, as well as multiple biochemical assays, were performed.
resultsDecreases in Pro-CoA and its derivative propionyl-L-carnitine due to ALDH6A1 downregulation were tightly associated with HCC. Functionally, ALDH6A1-mediated Pro-CoA metabolism suppressed HCC proliferation in vitro and impaired hepatocarcinogenesis in mice. The aldehyde dehydrogenase activity was indispensable for this function of ALDH6A1, while Pro-CoA carboxylases antagonized ALDH6A1 function by eliminating Pro-CoA. Mechanistically, ALDH6A1 caused a signature enrichment of central carbon metabolism in cancer and impaired energy metabolism: ALDH6A1-generated Pro-CoA suppressed citrate synthase activity, which subsequently reduced tricarboxylic acid cycle flux, impaired mitochondrial respiration and membrane potential, and decreased ATP production. Moreover, Pro-CoA metabolism generated 2-methylcitric acid, which mimicked the inhibitory effect of Pro-CoA on citrate synthase and dampened mitochondrial respiration and HCC proliferation.
conclusionsThe decline of ALDH6A1-mediated Pro-CoA metabolism contributes to metabolic remodeling and facilitates hepatocarcinogenesis. Pro-CoA, propionyl-L-carnitine and 2-methylcitric acid may serve as novel metabolic biomarkers for the diagnosis and treatment of HCC. Pro-CoA metabolism may provide potential targets for development of novel strategies against HCC. IMPACT AND IMPLICATIONS: Our study presents new insights on the role of propionyl-CoA metabolism in metabolic reprogramming and hepatocarcinogenesis. This work has uncovered potential diagnostic and predictive biomarkers, which could be used by physicians to improve clinical practice and may also serve as targets for the development of therapeutic strategies against HCC.
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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 OpenQuestion graph.