ArticleOncogene2023
A positive feedback between cholesterol synthesis and the pentose phosphate pathway rather than glycolysis promotes hepatocellular carcinoma.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- Suppression of macrophage membrane cholesterol efflux by SLAMF7-induced IL-7 signaling improves immunotherapy efficacy in hepatocellular carcinoma.Hepatology international · 2026Article
- A positive feedback loop between TKT and c-Myc drives TACE resistance in hepatocellular carcinoma.Cell death discovery · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Revisiting cholesterol metabolism in hepatocellular carcinoma: a hidden driver of systemic therapy response.ESMO gastrointestinal oncology · 2026Review
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Quercetin and Its Metabolites: Mechanistic Insights as the Basis of Their Therapeutic Potential in NAFLD and HCC.Molecules (Basel, Switzerland) · 2025Review
- Article
- The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.International journal of molecular sciences · 2025Review
- Instationary metabolic flux analysis reveals that NPC1 inhibition increases glycolysis and decreases mitochondrial metabolism in brain microvascular endothelial cells.Neurobiology of disease · 2025Article
- Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins.Frontiers in pharmacology · 2025Review
- Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- MicroRNA-206 as a potential cholesterol-lowering drug is superior to statins in mice.Journal of lipid research · 2024Article
- Review
- Pivotal role of intestinal cholesterol and nuclear receptor LXR in metabolic liver steatohepatitis and hepatocarcinoma.Cell & bioscience · 2024Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic cholesterol accumulation and hypercholesterolemia are implicated in hepatocellular carcinoma (HCC). However, the therapeutic effects of cholesterol-lowering drugs on HCC are controversial, indicating that the relationship between cholesterol metabolism and HCC is more complex than anticipated. A positive feedback between cholesterol synthesis and the pentose phosphate pathway (PPP) rather than glycolysis was formed in tumors of c-Myc mice. Blocking the PPP prevented cholesterol synthesis and thereby HCC in c-Myc mice, while ablating glycolysis did not affect cholesterol synthesis and failed to prevent c-Myc-induced HCC. Unexpectedly, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) and G6PD (glucose-6-phosphate dehydrogenase), the rate-limiting enzymes of cholesterol synthesis and the PPP, were identified as direct targets of microRNA-206. By targeting Hmgcr and G6pd, microRNA-206 disrupted the positive feedback and fully prevented HCC in c-Myc mice, while 100% of control mice died of HCC. Disrupting the interaction of microRNA-206 with Hmgcr and G6pd restored cholesterol synthesis, the PPP and HCC growth that was inhibited by miR-206. This study identified a previously undescribed positive feedback loop between cholesterol synthesis and the PPP, which drives HCC, while microRNA-206 prevents HCC by disrupting this loop. Cholesterol synthesis as a process rather than cholesterol itself is the major contributor of HCC.
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