The current article reports the investigation of three new Ni(II) complexes with ONS-donor dithiocarbazate ligands: [Ni(L¹)PPh₃] (1), [Ni(L²)PPh₃] (2), and [Ni(L²)Py] (3). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were π⋅⋅⋅π stacking interactions and non-classical hydrogen bonds C–H···H and C–H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC₅₀) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC₅₀ values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex (2) as a promising candidate for further therapeutic exploration.

SMYD4 is a member of the SMYD family that has lysine methyltransferase function. Little is known about the roles of SMYD4 in cancer. The aim of this study is to investigate genetic alterations in the SMYD4 gene across the most prevalent solid tumors and determine its potential as a biomarker. We performed an integrative multi-platform analysis of the most common mutations, copy number alterations (CNAs), and mRNA expression levels of the SMYD family genes using cohorts available at the Cancer Genome Atlas (TCGA), cBioPortal, and the Catalogue of Somatic Mutations in Cancer (COSMIC). SMYD genes displayed a lower frequency of mutations across the studied tumors, with none of the SMYD4 mutations detected demonstrating sufficient discriminatory power to serve as a biomarker. In terms of CNAs, SMYD4 consistently exhibited heterozygous loss and downregulation across all tumors evaluated. Moreover, SMYD4 showed low expression in tumor samples compared to normal samples, except for stomach adenocarcinoma. SMYD4 demonstrated a frequent negative correlation with other members of the SMYD family and a positive correlation between CNAs and mRNA expression. Additionally, patients with low SMYD4 expression in STAD and LUAD tumors exhibited significantly poorer overall survival. SMYD4 demonstrated its role as a tumor suppressor in the majority of tumors evaluated. The consistent downregulation of SMYD4, coupled with its association with cancer progression, underscores its potential usefulness as a biomarker.

SETD5 (SET domain-containing 5) is a chromatin-associated regulator increasingly recognized as dysregulated in human malignancies; however, its contribution to tumor biology and tumor–immune interactions remain undefined. We performed an integrative pan-cancer multi-omics analysis to define the landscape of SETD5 dysregulation across cancer types. Transcriptomic, genomic, and epigenetic datasets were integrated to evaluate SETD5 alterations and molecular associations. Protein interaction and pathway enrichment analyses were conducted using STRING, GO, and KEGG, and immunogenomic profiling was used to interrogate associations between SETD5 expression, immune infiltration, and checkpoint programs. SETD5 was overexpressed across multiple malignancies, with low mutation frequency but recurrent copy-number gains. Promoter hypomethylation was detected in a subset of tumors with increased SETD5 expression, suggesting a possible association with epigenetic regulation. Pathway analyses linked SETD5 to macromolecule methylation and transcriptional regulation. SETD5 expression correlated positively with infiltration of macrophages, neutrophils, and dendritic cells, whereas associations with CD8⁺ and CD4⁺ T cells varied by tumor type. Tumor type-specific correlations were observed between SETD5 and immune checkpoints genes, including PD-L1 and TIM-3, suggesting an association with immunoregulatory tumor states. These findings identify SETD5 as a recurrently deregulated epigenetic regulator and highlight its potential role in transcriptional control and tumor immune modulation.