Studies show that intracellular accumulation of copper ions causes cuproptosis, potentially enhancing anticancer immunity. However, the induction of cuproptosis inevitably faces challenges due to low intracellular copper deliver efficiency and collateral damage to normal tissues. This paper presents a self‐amplified cuproptosis nanoplatform (CEL NP) composed of Cu_2−XS hollow nanospheres (HNSs), elesclomol (ES), and phase‐change material lauric acid (LA). Under NIR‐II laser irradiation, the photothermal energy generated by Cu_2−XS HNSs melts LA, facilitating the precise release of ES and copper ions within the tumor microenvironment. Notably, ES can traverse the cell membrane and form ES‐Cu(II) complexes, thereby enhancing copper delivery within tumor cells. Excess Cu(II) also reacts with endogenous glutathione, reducing its inhibitory effect on cuproptosis. Ultimately, this amplified cuproptosis effect can activate immunogenic cell death, eliciting a robust immune response and promoting tumor suppression. The CEL NP‐mediated release of ES and copper ions offers a novel approach for anticancer therapy through cuproptosis induction.

Introduction: C-type lectin domain family 11 member A (CLEC11A) was characterized as a growth factor that mainly regulates hematopoietic function and differentiation of bone cells. However, the involvement of CLEC11A in gastric cancer (GC) is not well understood.Methods: Transcriptomic data and clinical information pertaining to GC were obtained and analyzed from publicly available databases. The relationships between CLEC11A and prognoses, genetic alterations, tumor microenvironment (TME), and therapeutic responses in GC patients were analyzed by bioinformatics methods. A CLEC11A-derived immune signature was developed and validated, and its mutational landscapes, immunological characteristics as well as drug sensitivities were explored. A nomogram was established by combining CLEC11A-derived immune signature and clinical factors. The expression and carcinogenic effects of CLEC11A in GC were verified by qRT−PCR, cell migration, invasion, cell cycle analysis, and in vivo model analysis. Myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and T cells in tumor samples extracted from mice were analyzed utilizing flow cytometry analysis.Results: CLEC11A was over-expressed in GC, and the elevated CLEC11A expression indicated an unfavorable prognosis in GC patients. CLEC11A was involved in genomic alterations and associated with the TME in GC. Moreover, elevated CLEC11A was found to reduce the benefit of immunotherapy according to immunophenoscore (IPS) and the tumor immune dysfunction, exclusion (TIDE). After validation, the CLEC11A-derived immune signature demonstrated a consistent ability to predict the survival outcomes in GC patients. A nomogram that quantifies survival probability was constructed to improve the accuracy of prognosis prediction in GC patients. Using shRNA to suppress the expression of CLEC11A led to significant inhibitions of cell cycle progression, migration, and invasion, as well as a marked reduction of in vivo tumor growth. Moreover, the flow cytometry assay showed that the knock-down of CLEC11A increased the infiltration of cytotoxic CD8+ T cells and helper CD4+ T into tumors while decreasing the percentage of M2 macrophages, MDSCs, and Tregs.Conclusion: Collectively, our findings revealed that CLEC11A could be a prognostic and immunological biomarker in GC, and CLEC11A-derived immune signature might serve as a new option for clinicians to predict outcomes and formulate personalized treatment plans for GC patients.

The present study aimed to investigate the biological function and relative mechanisms of circRNA_100876 in gastric cancer (GC). To this end, quantitative real-time polymerase chain reaction (RT-qPCR) was performed to examine the expression of circRNA_100876 and miR-665 in GC tissues and cells, and circRNA_100876 expression was depleted by the transfection of circ_100876-targeting siRNAs. CCK-8, flow cytometry, and Transwell assays were applied to examine GC cell cycle distribution, proliferation, apoptosis, migration, and invasion abilities. Proteins related to apoptosis and epithelial-mesenchymal transition (EMT) were detected by western blotting. Luciferase reporter assays were conducted to verify the direct target site between circRNA_100876 and miR-665. Our study confirmed that circRNA_100876 was highly expressed in GC lesions compared with the adjacent normal tissues (P < 0.001). High circRNA_100876 expression was negatively associated with survival outcome (P = 0.000). Furthermore, the down-regulation of circRNA_100876 could inhibit GC cell proliferation, invasion, and migration by suppressing the EMT pathway. Further study suggested that circRNA_100876 could act as a competing endogenous RNA by sequestering miR-665, and luciferase activity assay indicated that circRNA_100876 could bind directly with miR-665. Moreover, we found that Yes-associated protein 1 (YAP1) was the downstream target gene of miR-665, miR-665 knockdown could up-regulate YAP1 expression in MKN45 cells, and YAP1 knockdown could inhibit MKN45 cell proliferation, migration and invasion. Therefore, we demonstrated that circRNA_100876 over-expression in GC could promote GC tumor growth, migration and invasion and exert its effects through miR-665/YAP1 signaling.

Colorectal cancer (CRC) is a major global health challenge due to its high incidence and mortality rates. Understanding its epidemiological trends is essential for informing prevention and intervention strategies. This study analyzed global, regional, and national CRC data from 2010 to 2021, focusing on age-standardized incidence, mortality, disability-adjusted life years (DALY), and associated risk factors. Data was sourced from the Global Burden of Disease (GBD) Study 2021 and stratified by the Sociodemographic Index (SDI). Globally, CRC incidence increased by 35.91% from 1,614,410 cases in 2010 to 2,194,143 cases in 2021. The mortality rate decreased from 13.37 per 100,000 in 2010 to 12.40 per 100,000 in 2021. DALY increased by 23.94%, yet the age-standardized DALY rate (ASDR) decreased by 6.88%. Notably, high SDI regions showed a downward trend in incidence and mortality, while high-middle SDI regions experienced increasing incidence but decreasing mortality. In 2021, the highest incidence was in the Netherlands (69.80 per 100,000), and the highest mortality was in Uruguay (27.46 per 100,000). Dietary and metabolic risk factors significantly contributed to CRC burden across all SDI levels. The study reveals a complex epidemiological landscape of CRC, marked by rising incidence but declining mortality globally. These findings highlight the urgent need for targeted public health interventions, particularly in high-risk regions and younger populations, focusing on modifiable lifestyle and socioeconomic factors. Continuous monitoring and tailored prevention strategies are critical to reducing the global burden of CRC.

Background: This study aimed to explore the biological functions and prognostic role of Epithelial-mesenchymal transition (Epithelial-mesenchymal transition)-related lncRNAs in colorectal cancer (CRC).Methods: The Cancer Genome Atlas database was applied to retrieve gene expression data and clinical information. An EMT-related lncRNA risk signature was constructed relying on univariate Cox regression, Least Absolute Shrinkage and Selector Operation (LASSO) and multivariate Cox regression analysis of the EMT-related lncRNA expression data and clinical information. Then, an individualized prognostic prediction model based on the nomogram was developed and the predictive accuracy and discriminative ability of the nomogram were determined by the receiver operating characteristic curve and calibration curve. Finally, a series of analyses, such as functional analysis and unsupervised cluster analysis, were conducted to explore the influence of independent lncRNAs on CRC.Results: A total of 581 patients were enrolled and an eleven-EMT-related lncRNA risk signature was identified relying on the comprehensive analysis of the EMT-related lncRNA expression data and clinical information in the training cohort. Then, risk scores were calculated to divide patients into high and low-risk groups, and the Kaplan-Meier curve analysis showed that low-risk patients tended to have better overall survival (OS). Multivariate Cox regression analysis indicated that the EMT-related lncRNA signature was significantly associated with prognosis. The results were subsequently confirmed in the validation dataset. Then, we constructed and validated a predictive nomogram for overall survival based on the clinical factors and risk signature. Functional characterization confirmed this signature could predict immune-related phenotype and was associated with immune cell infiltration (i.e., macrophages M0, M1, Tregs, CD4 memory resting cells, and neutrophils), tumor mutation burden (TMB).Conclusions: Our study highlighted the value of the 11-EMT-lncRNA signature as a predictor of prognosis and immunotherapeutic response in CRC.

Objective: This study was performed to investigate the relationship among UHRF1 expression, its biological function and immune infiltration in human hepatocellular carcinoma (HCC). Methods: Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, and The Cancer Genome Atlas (TCGA) databases were used to analyze UHRF1 expression between HCC and normal tissues. Subsequently, GEPIA, TCGA-Portal, Kaplan–Meier Plotter, Protein Atlas and SurvExpress databases were utilized for survival analysis. UHRF1 co-expression genes were identified via the cBioPortal and LinkedOmics databases. Further, gene ontology (GO) analysis as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. Protein–protein interaction (PPI) networks was constructed by STRING database and Cytoscape 3.7.1. Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm were employed to assess the correlation between UHRF1 and tumor immune infiltrates on TCGA database. TIMER 2.0 database was used to explore the correlation of UHRF1 expression and immune infiltration level in HCC. Additionally, RT-qPCR was used to analyze the expression of UHRF1 and the relative genes in HCC cell lines. Results: Expression level of UHRF1 was upregulated in HCC tissues compared with paired normal tissues (P < 0.05 in GEPIA; P = 1.78E^{− 6} in Oncomine; and P < 0.0001 in TCGA). Its high expression was significantly related with a shorter overall survival in five databases (P < 0.05). Function enrichment analysis demonstrated that functions of UHRF1 concentrated in cell division process and cell cycle (P < 0.05). High UHRF1 expression exhibited dysregulated immune infiltration (ie, neutrophils, eosinophils, dendritic cells resting, macrophages M2, macrophages M0) and poor survival of high UHRF1 expression was tight correlated with immune infiltration status. Moreover, TP53 mutation can lead to high expression of UHRF1 (P = 4.2E^{− 10}). Conclusion: UHRF1 might function as an oncogene via inducing dysregulated immune infiltration in HCC and was identified as a novel prognostic biomarker and potential therapeutic target for HCC.