Integrated Proteomics and Metabolomics Analysis Provides Insights into Metformin Down-regulating GLUL and SP1 to Inhibit Esophageal Squamous Cell Carcinoma Migration and Invasion.

Unraveling role of arginine-NO metabolism by targeting HIF-1α signaling in mediating esophageal squamous cell carcinoma

It is confirmed that ESCC exhibits significant amino acid metabolic dysregulation, with arginine related metabolic pathways being significantly enriched, and NO can serve as a potential non-invasive biomarker for distinguishing ESCC.

Integrated proteomic profiling and in silico miRNA and lncRNA analysis of glucose-capped fisetin silver nanoparticle-mediated cell proliferation arrest in breast cancer

Integrative single-cell and multi-omics analysis of ZBTB21-mediated serine metabolism in colorectal cancer: from metabolic reprogramming to immune microenvironment modulation.

BACKGROUND Colorectal cancer (CRC) exhibits pronounced biological diversity, a feature increasingly attributed to alterations in cellular metabolic reprograms. Serine metabolism supports nucleotide synthesis, redox balance, and epigenetic regulation via one-carbon metabolism, yet its role in shaping the tumor cellular interactions and immune landscape at single-cell level remains unclear. METHODS Single-cell transcriptomic profiles (GSE284449) were jointly analyzed with bulk expression datasets (GSE271719), together with Mendelian randomization (MR)-based inference, to dissect serine metabolism in CRC. High-serine-metabolism (HSM) cell populations were identified using scMetabolism, and robust marker genes were selected through Lasso, random forest, XGBoost, and SVM-RFE machine learning approaches. MR was applied to evaluate causal associations with CRC risk. Functional validation included IHC, qRT-PCR, western blot, and LC-MS metabolomics, while CellChat analysis characterized HSM cell interactions with immune and stromal cells. RESULTS ZBTB21 and TRPM2 were identified as core regulators of HSM cells, with ZBTB21 predominantly expressed in monocytes and pro-B cells. MR analysis suggested a potential inverse association between genetically predicted ZBTB21 expression and CRC risk, indicating that ZBTB21 may exert context-dependent effects at the population level. Cell-cell communication analysis suggested that HSM monocytes may interact with fibroblasts through signaling pathways including the MIF-SPP1 axis; however, these interactions are computationally inferred and require further experimental validation. Functional assays showed that ZBTB21 overexpression upregulated PHGDH and SHMT1, increased intracellular NADPH/NADP⁺ ratios, and influenced monocyte-related phenotypes. ZBTB21 levels were markedly increased in CRC samples relative to matched non-tumorous mucosal tissues. CONCLUSIONS At single-cell resolution, ZBTB21 emerges as a metabolic regulator that strengthens serine biosynthesis and redox homeostasis. While integrative analyses suggest a potential link between ZBTB21-associated metabolic states and immune interactions, further experimental validation is required to establish causal relationships. This integrative framework connects genetic causality, metabolism, and immune interactions, providing mechanistic insights and potential strategies for metabolic-targeted therapies in CRC. TRIAL REGISTRATION Not applicable.

PPIB interacts with MET to activate the PI3K-AKT pathway and promote head and neck squamous cell carcinoma pathogenesis

Comprehensive Pan‐Cancer Analysis of ABCA1: Insights From Multi‐Omics Data and Exploratory Validation in Esophageal Squamous Cell Carcinoma

Cancer remains a major cause of global mortality, necessitating the identification of novel biomarkers to improve prognosis and guide therapy. ABCA1, an ATP‐binding cassette transporter involved in cholesterol efflux, has been implicated in tumorigenesis, yet its pan‐cancer roles and clinical relevance are not fully understood. We conducted a comprehensive multi‐omics analysis of ABCA1 across diverse cancers, evaluating its expression, prognostic significance, genomic alterations, tumor immune microenvironment interactions, and regulatory mechanisms. ABCA1 expression was dysregulated in multiple malignancies and associated with poor prognosis in STAD, STES, and LGG, though favorable outcomes were observed in KIRC. It correlated with genomic instability markers (TMB, MSI, HRD), immune cell infiltration, and cancer stemness. Pathway analyses revealed enrichment in cholesterol metabolism and efferocytosis‐related pathways. Among the cancer types examined, esophageal squamous cell carcinoma (ESCC) was selected for exploratory functional validation due to its prognostic relevance. In vitro, ABCA1 knockdown inhibited proliferation, invasion, and migration in ESCC cell lines. In silico drug sensitivity analysis suggested potential associations with dasatinib response and panobinostat resistance, warranting further experimental validation. Collectively, these findings highlight the context‐dependent associations of ABCA1 with cancer progression, immune modulation, and genomic integrity, suggesting its potential utility as a prognostic biomarker that warrants further investigation for therapeutic targeting.

Integration of miRNA profiling and proteomics to determine the target(s) implicated in endometrial cancer cells exposed to zearalenone.

Zearalenone (ZEA), a natural estrogenic mycotoxin, can cause serious harmful effects on human and animal health. Several studies have reported that ZEA induces proliferation in endometrial cancer; however, its role in modulating microRNA (miRNA) and protein expression profiles remains poorly established. This study investigates the effects of low-dose ZEA exposure on endometrial cancer cells using an integrated approach combining miRNA and proteome profiling. Ishikawa cells were exposed to 25 nM ZEA or 10 nM 17-β-estradiol (E2) for 10 days. miRNA profiling using a customized cancer-specific 56-miRNA array panel revealed significant alterations in miRNA expression, with miR-204 highly upregulated in both the E2 and ZEA treatment groups. For the global protein profiling, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed. Proteomics analysis identified 243 upregulated and 227 downregulated proteins following ZEA exposure, and, in the case of E2, 286 were upregulated and 123 were downregulated. Notably, miR-204 upregulation correlated with the downregulation of three target proteins: RETSAT, IPO8, and LRRC59. Gain- and loss-of-function studies using miR-204 mimics and inhibitors confirmed its role in promoting cell proliferation, growth, and migration. The present study provides novel insights into the molecular mechanism underlying ZEA-induced promotion of endometrial cancer, highlighting the potential role of miR-204 as a key mediator. Our findings contribute to understanding the role of environmental factors in cancer development and may inform future strategies for the prevention and treatment of endometrial cancer.