Search Results (3)

Background/Objectives: Endometrial cancer (EC) is a heterogeneous gynecological malignancy characterized by varied clinical outcomes and complex molecular mechanisms. The dysregulation of cyclin K (CCNK), a key regulator of transcription and cell cycle progression, has been implicated in cancer development. This study aimed to investigate CCNK expression at the protein level in EC tissues and at the mRNA level using in silico analysis. Additionally, the prognostic significance of CCNK expression in EC was assessed. Methods: CCNK expression was evaluated using immunohistochemical analysis and mRNA expression profiling in EC tissues, adjacent non-tumorous tissues, and histologically normal endometrial tissues. Immunohistochemical staining was performed on tissue macroarrays, and protein expression was quantified using the Immunoreactivity Score (IRS). mRNA expression analysis was conducted in silico using TCGA data via UCSC Xena and UALCAN web tool. Pathway enrichment was analyzed using Reactome and DAVID tool, while PPI networks were constructed with STRING and Cytoscape. Statistical analyses, including Mann–Whitney U test, Fisher’s exact test, Chi-square test, Kaplan–Meier survival analysis, and Cox regression, were performed using GraphPad Prism. Results: Immunohistochemical analysis revealed significantly elevated CCNK protein expression in tumor tissues, particularly in advanced-stage cases, correlating with adverse pathological features such as higher tumor stage and FIGO grade. High CCNK protein expression was significantly associated with poorer OS in the overall EC cohort and non-endometrioid subtypes, whereas no significant association was observed in endometrioid subtypes. mRNA expression analysis demonstrated significantly higher CCNK levels in non-endometrioid tumors compared to adjacent non-tumorous tissues, but no significant correlation with OS was observed. Functional enrichment analysis highlighted the involvement of CCNK-associated genes in RNA metabolism and transcriptional regulation. Conclusions: These findings emphasize the prognostic value of CCNK expression in EC, particularly in aggressive subtypes. The results suggest that CCNK may serve as a potential therapeutic target, warranting further investigation into its role in EC progression and treatment strategies. Full article

Cardiac glycosides (CGs) constitute a group of steroid-like compounds renowned for their effectiveness in treating cardiovascular ailments. In recent times, there has been growing recognition of their potential use as drug leads in cancer treatment. In our prior research, we identified three highly promising CG compounds, namely lanatoside C (LC), peruvoside (PS), and strophanthidin (STR), which exhibited significant antitumor effects in lung, liver, and breast cancer cell lines. In this study, we investigated the therapeutic response of these CGs, with a particular focus on the MCF-7 breast cancer cell line. We conducted transcriptomic profiling and further validated the gene and protein expression changes induced by treatment through qRT-PCR, immunoblotting, and immunocytochemical analysis. Additionally, we demonstrated the interactions between the ligands and target proteins using the molecular docking approach. The transcriptome analysis revealed a cluster of genes with potential therapeutic targets involved in cytotoxicity, immunomodulation, and tumor-suppressor pathways. Subsequently, we focused on cross-validating the ten most significantly expressed genes, EGR1, MAPK1, p53, CCNK, CASP9, BCL2L1, CDK7, CDK2, CDK2AP1, and CDKN1A, through qRT-PCR, and their by confirming the consistent expression pattern with RNA-Seq data. Notably, among the most variable genes, we identified EGR1, the downstream effector of the MAPK signaling pathway, which performs the regulatory function in cell proliferation, tumor invasion, and immune regulation. Furthermore, we substantiated the influence of CG compounds on translational processes, resulting in an alteration in protein expression upon treatment. An additional analysis of ligand–protein interactions provided further evidence of the robust binding affinity between LC, PS, and STR and their respective protein targets. These findings underscore the intense anticancer activity of the investigated CGs, shedding light on potential target genes and elucidating the probable mechanism of action of CGs in breast cancer. Full article

The terminal 14q32 duplication has been reported often in association with other cytogenetic abnormalities, and individuals with this specific duplication showed varying degrees of developmental delay/intellectual disability (DD/ID) and growth retardation (GR), and distinct facial dysmorphisms. Herein, based on the limited cases of terminal duplication of 14q32 known to date, we present new affected siblings presenting with DD/ID, GR, and facial dysmorphism, as well as cerebral infarction caused by recurrent de novo der(14)t(14;14)(p11.2;q32.1) leading to terminal duplication of 14q32. We used coverage analysis generated via duo exome sequencing, performed chromosomal microarray (CMA) as a confirmatory test, and compared our findings with those reported previously. Coverage analysis generated via duo exome sequencing revealed a 17.2 Mb heterozygous duplication at chromosome 14q32.11-q32.33 with a Z ratio ranging between 0.5 and 1 in the proband and her elder brother. As a complementary method, CMA established a terminal duplication described as the arr[hg19]14q32.11q32.33(90,043,558_107,258,824)x3 in the proband and her elder brother; however, the parents and other siblings showed normal karyotyping and no abnormal gain or loss of CMA results. Five candidate genes, BCL11B, CCNK, YY1, DYNC1H1, and PACS2, were associated with the clinical phenotypes in our cases. Although the parents had normal chromosomes, two affected cases carrying terminal duplication of 14q32 can be explained by gonadal mosaicism. Further studies are needed to establish the association between cerebrovascular events and terminal duplication of chromosome 14q32, including investigation into the cytogenetics of patients with precise clinical descriptions. Full article