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Objective To investigate the role of ATP citrate lyase(ACLY)in the development of hepatocellular carcinoma(HCC)and the impact of this enzyme on the immune microenvironment of HCC.Methods We utilized the University of Alabama at Birmingham Cancer Data Analysis Portal and the Gene Expression Profiling Interactive Analysis to identify the changes in ACLY expression and prognosis across different tumor types from The Cancer Genome Atlas.With HCC as the disease model,we analyzed the ACLY expression in HCC samples from the gene expression database.Furthermore,we collected the clinical specimens from HCC patients to verify the mRNA and protein levels of ACLY.In addition,we conducted transcriptome sequencing after knocking down the expression of ACLY to analyze the differentially expressed genes and investigated the impact of ACLY expression interference on cell proliferation and other functions.Finally,we explored the correlations of ACLY with immune cells and immune infiltration in the tumor microenvironment,new antigens,and immune checkpoint genes.Results ACLY expression was significantly up-regulated in solid tumors including HCC(all <0.05),and high ACLY expression was associated with overall survival rate in HCC(=0.005).Furthermore,high ACLY expression affected the presence of immune cells(e.g.,tumor-associated fibroblasts)and the expression of genes involved in lipid metabolism(all <0.05).Conclusions ACLY is closely related to the occurrence and development of HCC and lipid metabolism abnormalities.Moreover,it has a specific impact on the immune microenvironment of HCC.
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http://dx.doi.org/10.3881/j.issn.1000-503X.15590 | DOI Listing |
Int Immunopharmacol
September 2025
Cancer Center and Center of Translational Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China. Electronic address:
Ring finger protein 180 (RNF180) is an E3 ubiquitin-protein ligase that promotes polyubiquitination and degradation. We analyzed the roles and molecular mechanisms of RNF180 during the tumorigenesis and progression of colorectal cancer (CRC) through bioinformatics analysis, in vivo and vitro experiments. RNF180 overexpression was observed in CRC, and positively associated with T, N and TNM staging or differentiation.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
July 2025
Jiangxi Province Key Laboratory of Traditional Chinese Medicine Etiopathogenisis & Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory, Jiangxi University of Chinese Medicine Nanchang 330004, China.
This study aims to investigate the in vitro mechanisms underlying the beneficial effects of puerarin on hepatic insulin resistance(IR) based on the carbohydrate response element-binding protein(ChREBP)/peroxisome proliferator-activated receptor(PPAR)α/PPARγ axis involved in glucose and lipid metabolism. An IR-HepG2 cell model was established by treating cells with dexamethasone for 48 h, and the cells were then treated with 10, 20, and 40 μmol·L~(-1) puerarin for 24 h. Glucose levels and output in the extracellular fluid were measured by the glucose oxidase method, while cell viability was assessed by the cell counting kit-8(CCK-8) assay.
View Article and Find Full Text PDFSignal Transduct Target Ther
September 2025
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
Lymph node metastasis is crucial for esophageal squamous cell carcinoma (ESCC) malignancy. However, the molecular drivers and related mechanisms of lymph node metastasis in ESCC cells are unclear. In the present study, we found that the tyrosine kinase complex-focal adhesion kinase (FAK)/Src family kinase (SFK) axis specifically contributes to metabolic reprogramming by inducing the phosphorylation of ATP-citrate synthase (ACLY) Tyr542, Tyr652, and fructose-bisphosphate aldolase A (ALDOA) Tyr174, Tyr302, or Tyr328 sites in both primary and metastatic ESCC cells.
View Article and Find Full Text PDFCancer Immunol Immunother
August 2025
Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
The prognosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor. Therefore, searching for new therapeutic agents is particularly important to improve therapeutic efficacy. Targeting the ubiquitin-proteasome system is a potential therapeutic strategy for treating DLBCL.
View Article and Find Full Text PDFJ Immunol
August 2025
Department of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Natural killer (NK) cells are innate immune lymphocytes important for host viral and tumor immunity. We investigated the requirement for ATP citrate lyase (ACLY) in NK cell function using an inducible genetic mouse model. ACLY regulates the citrate-malate shuttle, generating cytosolic acetyl-coenzyme A that is primarily used for acetylation or lipid synthesis.
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