ArticleJHEP reports : innovation in hepatology2023
Loss of hepatic FTCD promotes lipid accumulation and hepatocarcinogenesis by upregulating PPARγ and SREBP2.
Article in JHEP reports : innovation in hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 26 citations in OpenAlex.
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- CircRPPH1 promotes hepatocellular carcinoma progression through inhibiting PPARα transcription and accelerating its ubiquitination and degradation.Cellular and molecular life sciences : CMLS · 2026Article
- Multi-omics integration analysis reveals metabolic changes during sika deer antler growth.BMC genomics · 2026Article
- Molecular classification and construction of prognostic risk model via machine learning based on metabolic-related genes in hepatocellular carcinoma.Translational cancer research · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Identification of Molecular Subtypes for Hepatocellular Carcinoma Based on Ubiquitin-Conjugating Enzyme E2 (UBE2)-Related Genes to Assess Prognosis and Immune Landscape.Immunity, inflammation and disease · 2026Article
- SREBP2 confers ferroptosis resistance by targeting GPX4 in colorectal cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Identification ofEndocrine, metabolic & immune disorders drug targets · 2026Article
- Combined analysis of metabolomics and transcriptomics reveals new indicators for the diagnosis and prognosis of colorectal cancer.Contemporary oncology (Poznan, Poland) · 2026Article
- SREBP2 as a Novel Biomarker for Posttransplant Hepatocellular Carcinoma Recurrence: A New Prognostic Nomogram.BioMed research international · 2026Article
- Multi-omics and machine learning refine HCC molecular subtypes and prognosis based on liquid-liquid phase separation related genes.Scientific reports · 2025Article
- Unsupervised Clustering Subtype Analysis and Prognostic Risk Model of Cuproptosis-Related Genes for Liver Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Obesity-Induced MASLD Is Reversed by Capsaicin via Hepatic TRPV1 Activation.Current issues in molecular biology · 2025Article
- Hepatitis B Virus X Protein Upregulates SREBP2 to Modulate Autophagy in Hepatocellular Carcinoma.Cancer medicine · 2025Article
- Multiple machine learning algorithms identified SLC6A8 as a diagnostic biomarker of the late stage of Hepatocellular carcinoma.Discover oncology · 2025Article
- Integrative Multi-Omics Approaches Reveal Selectivity Profiles and Molecular Mechanisms of FIIN-2, a Covalent FGFR Inhibitor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- New insights into T cell metabolism in liver cancer: from mechanism to therapy.Cell death discovery · 2025Review
- Utilizing liquid-liquid biopolymer regulators to predict the prognosis and drug sensitivity of hepatocellular carcinoma.Biology direct · 2025Article
- The role of PPARγ in cancer cachexia: friend or foe?Frontiers in endocrinology · 2025Review
- Identification of key genes associated with perineural invasion in stage II colorectal cancer and their prognostic implications.Frontiers in oncology · 2025Article
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Authors and funding
25 authors at 5 institutions in 2 countries.
Funding
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Abstract
Background & Aims: Exploiting key regulators responsible for hepatocarcinogenesis is of great importance for the prevention and treatment of hepatocellular carcinoma (HCC). However, the key players contributing to hepatocarcinogenesis remain poorly understood. We explored the molecular mechanisms underlying the carcinogenesis and progression of HCC for the development of potential new therapeutic targets. Methods: The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and Genotype-Tissue Expression (GTEx) databases were used to identify genes with enhanced expression in the liver associated with HCC progression. A murine liver-specific Results: FTCD is highly expressed in the liver but significantly downregulated in HCC. Patients with HCC and low levels of FTCD exhibited worse prognosis, and patients with liver cirrhosis and low FTCD levels exhibited a notable higher probability of developing HCC. Hepatocyte-specific knockout of FTCD promoted both chronic diethylnitrosamine-induced and spontaneous hepatocarcinogenesis in mice. Multi-omics analysis showed that loss of FTCD affected fatty acid and cholesterol metabolism in hepatocarcinogenesis. Mechanistically, loss of FTCD upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element-binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis. Conclusions: Taken together, we identified a FTCD-regulated lipid metabolic mechanism involving PPARγ and SREBP2 signaling in hepatocarcinogenesis and provide a rationale for therapeutically targeting of HCC driven by downregulation of FTCD. Impact and implications: Exploiting key molecules responsible for hepatocarcinogenesis is significant for the prevention and treatment of HCC. Herein, we identified formimidoyltransferase cyclodeaminase (FTCD) as the top enhanced gene, which could serve as a predictive and prognostic marker for patients with HCC. We generated and characterised the first
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