Aim: Active changes in neuronal DNA methylation and demethylation appear to act as controllers of synaptic scaling and glutamate receptor trafficking in learning and memory formation. DNA methyltransferases (DNMTs), including proteins encoded by Dnmt1, Dnmt3a and Dnmt3b, are dominant enzymes carrying out DNA methylation. Our previous study demonstrated the important roles that DNMT1 and DNMT3a play in synaptic function and memory. In this study, we aim to explore the role of DNMT3b and its-mediated DNA methylation in memory processes. Methods: Dnmt3b was knocked down specifically in dorsal CA1 neurons of adult mice hippocampus by AAV-syn-Cre-GFP virus injection. Behavioral tests were used to evaluate memory performance. Gene expression microarray analysis followed by quantitative RT-PCR were performed to find differential expression genes. Results: Dnmt3b flox/flox mice receiving Cre-virus infection showed impaired novel object-place recognition (NPR) and normal novel object recognition (NOR), in comparison to mice receiving control GFP-virus infection. Microarray analysis revealed differential expression of K + channel subunits in the hippocampus of Dnmt3b flox/flox mice receiving Cre-virus injection. Increased Kcne2 expression was confirmed by following qRT-PCR analysis. We also found that NPR training and testing induced up-regulation of hippocampal Dnmt1 and Dnmt3a mRNA expression in control mice, but not in Cre-virus injected mice. Our findings thus demonstrate that conditional Dnmt3b deletion in a subregion of the hippocampus impairs a specific form of recognition memory that is hippocampus-dependent.

The most common pathological subtype of renal carcinoma is RCC, and its development is closely related to immune infiltration. In our study, we investigated the relationship between zinc finger protein 668 and the prognostic risk, clinical characteristics, overall survival and related pathways. We analyzed the association between ZNF668 and immune cell infiltration through the TIMER database. The results showed that the expression of ZNF668 in RCC was higher than that in normal tissues (P < 0.001). The high expression of ZNF668 is clinically relevant, such as tumor stage (P = 0.001) and TNM classification (T: P = 7.37 e-04; N: P = 0.008; M: P < 0.001). Survival analysis showed that patients with high ZNF668 expression had a significantly poor prognosis (P = 0.023). Univariate analysis showed a significant decrease in overall survival in RCC patients with high ZNF668 expression (P = 0.023). Immuno-cell infiltration showed a significant decrease in CD4 + T cell and dendritic cell infiltration in RCC patients with high expression of ZNF668. GO/KEGG analysis showed that multiple pathways were differentially enriched in the high expression pathway of ZNF668, such as complement activation, and estrogen signaling pathway. In conclusion, high ZNF668 expression is a predictor in RCC. Anti-Cancer Drugs 33: e491-e499

MRG-binding protein (MRGBP) is a transcription factor widely involved in physiological and pathological processes. Many studies have discussed the relationship between the expression level of MRGBP and the prognosis of various malignant tumours. However, the role and clinicopathological significance of MRGBP in head and neck squamous cell carcinoma (HNSC) are unclear. In this study, the Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between clinical characteristics and MRGBP expression in HNSC. The Kaplan-Meier plotter analysis and Cox regression analysis were established to evaluate the effect of MRGBP on prognosis, and the receiver operating characteristic (ROC) curve and nomogram was constructed. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were used to analyze the correlation between MRGBP and immune infiltration. The results showed that the expression of MRGBP in HNSC tissues was significantly higher than that in normal tissues. The KM plotter analysis showed that the OS of HNSC patients was shorter. The multivariate Cox analysis further confirmed that increased expression of MRGBP was an independent risk factor for OS in HNSC patients. In addition, ROC analysis confirmed its diagnostic value and constructed prognostic nomograms, including age, T, M, N classification, pathological stage, and MRGBP. GSEA showed that MRGBP was associated with high expression of GPCR ligand binding, interleukin receptor binding, and neutrophil degranulation, and ssGSEA showed that MRGBP was associated with T cells and mast cells. In conclusion, MRGBP can serve as an independent prognostic biomarker related to immune invasion of head and neck squamous cell carcinoma.

Cuproptosis, the current form of regulated cell death characterized by copper overload, oligomerization of lipoacylated proteins, and loss of the Fe-S cluster proteins, has been proposed to function closely with human diseases including cancer. Since the first identification in 2022, a wide range of strategies have been developed to induce cuproptosis for cancer therapy, such as small-molecule drugs and nanomaterials. Although many reviews related to cuproptosis have been reported, they remain at a basic mechanism level and a summary covering recent progress in the field of nanotechnologies in cuproptosis-based cancer therapy has not yet been presented. Therefore, it is time to fill the gap and shed light on future directions for the application of this promising tool to fight against cancer. In this minireview, we first expounded the mechanism of action of cuproptosis and emphasized the feasibility of triggering cuproptosis for cancer therapy. The recent progress of cancer treatments based on nanoparticle-induced cuproptosis was then described. Finally, the challenges and future development directions of the emerging field of cuproptosis were also discussed.