Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 14, 2024

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types and represents a significant proportion esophageal cancer. Metabolic reprogramming plays key role in occurrence development ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid MPC3-energy based on enrichment scores metabolic pathways extracted from Reactome database. The MPC3 cluster exhibited characteristics energy metabolism, with heightened glycolysis, cofactors, nucleotide showing trend toward increased aggressiveness poorer survival rates. On other hand, MPC1 MPC2 primarily involved lipid amino respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles potential therapeutic agents were explored compared among lines different MPCs. amplified metabolism markers, especially carnitines. contrast, predominantly had elevated levels lipids (primarily triacylglycerol) acids, Furthermore, demonstrated suboptimal clinical response PD-L1 immunotherapy but showed sensitivity doramapimod chemotherapy regimen, as evident drug evaluations. These insights pave way for more personalized approach, potentially enhancing treatment precision patients.

Language: Английский

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A novel lung cancer stem cell extracellular vesicles lncRNA ROLLCSC modulate non-stemness cancer cell plasticity through miR-5623-3p and miR-217-5p targeting lipid metabolism

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 256, P. 128412 - 128412

Published: Nov. 27, 2023

Language: Английский

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LncRNA SNHG14/miR‐497a‐5p/BACE1 axis modulates obesity‐induced adipocyte inflammation and endoplasmic reticulum stress

Journal of Biochemical and Molecular Toxicology, Journal Year: 2023, Volume and Issue: 37(6)

Published: April 3, 2023

Obesity is a metabolic disease with excess weight. LncRNA SNHG14 abnormally expressed in numerous diseases. This research aimed to enucleate the lncRNA role obesity. Adipocytes were treated free fatty acid (FFA) establish an vitro model for Mice fed high-fat diet construct vivo model. Gene levels determined using quantitative real-time PCR (RT-PCR). The protein level was checked by western blot. obesity assessed blot and enzyme-linked immunosorbent assay. mechanism estimated Starbase, dual-luciferase reporter gene assay, RNA pull-down. function mouse xenograft models, RT-PCR, blot, BACE1 increased, but miR-497a-5p decreased FFA-induced adipocytes. Interference reduced endoplasmic reticulum (ER) stress-related molecules GRP78 CHOP expressions adipocytes, IL-1β, IL-6, TNF-α expressions, indicating that knockdown mitigated ER stress inflammation Mechanistically, combined miR-497a-5p, targeted BACE1. Meanwhile, of GRP78, CHOP, TNF-α, while cotransfection anti-miR-497a-5p or pcDNA-BACE1 abolished these trends. Rescue assays illustrated relieved adipocyte through miR-497a-5p/BACE1. restrained adipose caused vivo. mediated obesity-induced

Language: Английский

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AP001885.4 promotes the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc

Animal Cells and Systems, Journal Year: 2024, Volume and Issue: 28(1), P. 536 - 550

Published: Nov. 1, 2024

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, absolutely unclear. The GEPIA database was applied identify differentially expressed prognosis-associated genes esophageal cancer (ESCA). CCK-8, colony formation, Western blot, qRT-PCR methods were harnessed investigate mechanism carcinogenesis. By analyzing TCGA data database, two lncRNAs selected. overexpressed positively associated with unfavorable outcome ESCC patients, LINC001786 under-expressed negatively linked poor prognosis. Knockdown suppressed proliferation formation cells. Importantly, silence downregulated c-myc. Mechanically, knockdown reduced METTL3 expression m6A modification c-myc mRNA, regulated Furthermore, diminished histone lactylation NF-κB (p65) expression, protein inhibitors (2-DG, 2-deoxy-D-glucose oxamate) inhibitor (JSH-23) also lessened expression. Consequently, our findings suggested that promoted cells by lactylation- (p65)-dependent transcription activation METTL3-mediated mRNA stability

Language: Английский

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Prognostic significance and immune landscape of a fatty acid metabolism-related gene signature in colon adenocarcinoma

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 9, 2022

Background: Fatty acid metabolism (FAM), as a hallmark of caner, plays important roles in tumor initiation and carcinogenesis. However, the significance fatty metabolism-related genes colon adenocarcinoma (COAD) are largely unknown. Methods: RNA sequencing data clinical information were downloaded from Cancer Genome Atlas (TCGA) cohort. Univariate multivariate Cox regression analyses utilized to construct gene signature. Kaplan-Meier survival receiver operating characteristic (ROC) used verify performance this GEO datasets applied validate Maftools package was analyze mutation profiles Correlation between risk signature stemness scores compared by score (RNAss). Gene Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG) set variation analysis (GSVA) performed explore potential functions signaling pathways. Immune landscape explored analyzing different immune cells infiltration, microsatellite instability. A nomogram constructed combining multiple factors. Expression levels prognostic values revealed cancer genome atlas databases. Moreover, expression measured cell lines using real time quantitative PCR (qRT-PCR). Results: Eight (CD36, ENO3, MORC2, PTGR1, SUCLG2, ELOVL3, ELOVL6 CPT2) This demonstrated better value than other clinicopathological parameters, with AUC 0.734 according database. There negative correlation riskscore score. The patients high-risk group higher infiltration M0 macrophages, less activated CD4 memory T Eosinophils. more MSI those low-risk (38% vs. 30%). slightly stability group. ontology, kyoto encyclopedia genomes enrichment showed that several pathways enriched. good predictive capability qRT-PCR upregulated SUCLG2 ELOVL6, downregulated CPT2 all examined lines. Conclusion: study provided novel insights into prognosis an patients.

Language: Английский

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Identification of a Prognostic Gene Signature Based on Lipid Metabolism-Related Genes in Esophageal Squamous Cell Carcinoma

Pharmacogenomics and Personalized Medicine, Journal Year: 2023, Volume and Issue: Volume 16, P. 959 - 972

Published: Nov. 1, 2023

Dysregulation of lipid metabolism is common in cancer. However, the molecular mechanism underlying esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are not well understood. The objective our study was to construct a metabolism-related prognostic model improve prediction ESCC.We downloaded mRNA expression profiles corresponding survival data patients with ESCC from Gene Expression Omnibus (GEO) Cancer Genome Atlas (TCGA) databases. We performed differential analysis identify differentially expressed genes (DELMGs). used Univariate Cox regression least absolute shrinkage selection operator (LASSO) analyses establish risk GEO cohort TCGA for validation. also explored relationship between immune microenvironment via infiltrated cells checkpoints.The result showed that 132 unique DELMGs distinguished controls. identified four (ACAA1, ACOT11, B4GALNT1, DDHD1) as gene signatures model. Patients were classified into high- low-risk groups per signature-based score. receiver operating characteristic (ROC) curve Kaplan-Meier (KM) validate predictive performance 4-gene signature both training validation sets. Infiltrated checkpoints indicated difference status two groups.The results based related useful ESCC.

Language: Английский

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Long non‑coding RNAs, lipid metabolism and cancer (Review)

Experimental and Therapeutic Medicine, Journal Year: 2023, Volume and Issue: 26(4)

Published: Aug. 17, 2023

Cancer has emerged as the most common cause of death in China. The change lipid metabolism been confirmed to have a role several tumor types, such esophageal, gastric, colorectal and liver cancer. cells use for energy then rapidly proliferate, invade migrate. main pathway by which cancer cell influences progression is increased fatty acid synthesis. Long non‑coding (lnc)RNAs are important ncRNAs that were indicated significant roles development human tumors. They considered potential biomarkers. Increased synthesis or uptake due deregulation lncRNAs contributes rapid growth. In present review, current studies on relationship between lncRNAs, occurrence tumors collated summarized, their mechanism action was discussed. review expected provide theoretical basis treatment prognosis evaluation based effective regulation metabolism.

Language: Английский

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FAP positive cancer-associated fibroblasts promote tumor progression and radioresistance in esophageal squamous cell carcinoma by transferring exosomal lncRNA AFAP1-AS1

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 5, 2023

Abstract Background Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in the tumor microenvironment, which play important roles regulating progression therapy resistance by transferring exosomes to cancer cells. However, how CAFs modulate esophageal squamous cell carcinoma (ESCC) radioresistance remains incompletely understood. Methods The expression of fibroblast activation protein (FAP) was evaluated immunohistochemistry 174 ESCC patients who underwent surgery 78 pretreatment biopsy specimens definitive chemoradiotherapy. We sorted according FAP expression, conditioned medium (CM) collected culture levels several lncRNAs that were considered regulate and/or measured derived from + – CAFs. Subsequently, counting kit-8, EdU, transwell, colony formation, xenograft assays performed investigate functional differences between Finally, a series vitro vivo used evaluate effect AFAP1-AS1 on radiosensitivity Results positively correlated with nerve invasion, vascular depth lymph node metastasis, lack clinical complete response poor survival. Culture CM/FAP significantly increased proliferation, migration, invasion radioresistance, compared Importantly, exert their directly lncRNA via exosomes. Functional studies showed promoted enhancing DNA damage repair Clinically, high plasma responses dCRT patients. Conclusions Our findings demonstrated through exosomal AFAP1-AS1; may be potential therapeutic target for treatment.

Language: Английский

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Histone Chaperones and Digestive Cancer: A Review of the Literature

Cancers, Journal Year: 2022, Volume and Issue: 14(22), P. 5584 - 5584

Published: Nov. 14, 2022

The global burden of digestive cancer is expected to increase. Therefore, crucial for the prognosis patients with these tumors identify early diagnostic markers or novel therapeutic targets. There accumulating evidence connecting histone chaperones pathogenesis cancer. Histone are now broadly defined as a class proteins that bind histones and regulate nucleosome assembly. Recent studies have demonstrated multiple aberrantly expressed distinct roles in cancers.The purpose this review present current regarding role cancer, particularly their mechanism development progression esophageal, gastric, liver, pancreatic, colorectal cancers. In addition, prognostic significance particular discussed.According PRISMA guidelines, we searched PubMed, Embase, MEDLINE databases on from inception until June 2022.A total 104 involving 21 were retrieved.This confirms mechanisms selected suggests potential biomarkers However, due non-specificity, more research should be conducted future elucidate strategies treatment

Language: Английский

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Regulation of lipid and serine metabolism by the oncogene c-Myc

International review of cell and molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 236 - 256

Published: Jan. 1, 2024

Language: Английский

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