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(1) Background: Meningiomas are the most common intracranial tumors in adults; currently there is no effective chemotherapy for malignant meningiomas. The effect of disulfiram (DSF)/Copper (Cu) on meningiomas remains unclear; (2) Methods: The impact of DSF/Cu on cell viability of meningioma adhesion cells (MgACs) and sphere cells (MgSCs) was assessed via MTS assay. The effects of DSF/Cu on intracellular Cu levels, cell senescence, and apoptosis were analyzed using CopperGreen, C12FDG, and Annexin V assays. Intracellular ALDH isoform expression and canonical pathway expression after DSF/Cu treatment were analyzed using mRNA microarray and Ingenuity Pathway Analysis, with further verification through qRT-PCR and immunoblotting; (3) Results: The viability of MgACs and MgSCs were inhibited by DSF/Cu. DSF/Cu increased intracellular Cu levels and cellular senescence. DSF/Cu also induced ER stress in MgACs and activated the PERK/eIF2 pathway for further adaptive response, apoptosis, and autophagy. Finally, DSF/Cu inhibited the expression of different ALDH isoforms in MgACs and MgSCs; (4) Conclusions: DSF/Cu exerts cytotoxic effects against both meningioma cells and stem-like cells and has treatment potential for meningioma. [ABSTRACT FROM AUTHOR]

Immune checkpoints regulate immunity to prevent autoimmunity and protect the host from damage during pathogenic infection. They also participate in subverting immune surveillance and promote antitumor immunity in cancers. Although immunotherapy improves clinical outcomes, not all cancer patients experience expected responses after therapy. Hence, it would be meaningful to explore crucial immune checkpoints in cancers for future immunotherapies. By analyzing pan-cancer data in The Cancer Genome Atlas (TCGA), cluster of differentiation 276 (CD276), also known as B7H3 , was found to be a risk gene in several cancers. A positive correlation existed between CD276 and natural killer (NK) cell infiltration. Overexpression of CD276 attenuated NK cell-mediated cell killing. Furthermore, CD276 levels showed a significant negative association with microRNA (miR)-29c-3p. Overexpression of miR-29c-3p rescued CD276-reduced NK cell cytotoxicity. According to gene set enrichment analyses , CD276-associated genes were found to be enriched in genes that targeted Myc. A negative correlation existed between miR-29 expression and Myc activity. CD276 enhanced Myc phosphorylation levels while suppressing miR-29c-3p expression. In contrast, miR-29c-3p inhibited CD276 expression, leading to reduced Myc activity. Myc suppressed miR-29c-3p expression while promoting CD276 upregulation. These findings suggest that a negative regulatory loop among CD276, Myc, and miR-29c-3p influences cancer cells against NK cell cytotoxicity. [Display omitted] • CD276, a risk gene in cancers, is related to NK cell infiltration and attenuated NK cell-mediated cell killing. • miR-29c-3p targets to CD276 and rescues CD276-reduced NK cell cytotoxicity. • A negative regulatory loop among CD276, Myc, and miR-29c-3p exists in tumors escaping from an immune response. [ABSTRACT FROM AUTHOR]