Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods: DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.
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http://dx.doi.org/10.3390/cancers12113439 | DOI Listing |
Unlabelled: Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, more effective, and less toxic therapies.
View Article and Find Full Text PDFNeuro Oncol
June 2024
Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Background: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype.
View Article and Find Full Text PDFNeuro Oncol
March 2024
Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Background: Pediatric high-grade gliomas (PHGG) are aggressive brain tumors with 5-year survival rates ranging from <2% to 20% depending upon subtype. PHGG presents differently from patient to patient and is intratumorally heterogeneous, posing challenges in designing therapies. We hypothesized that heterogeneity occurs because PHGG comprises multiple distinct tumor and immune cell types in varying proportions, each of which may influence tumor characteristics.
View Article and Find Full Text PDFActa Neuropathol Commun
September 2023
Department of Pathology, University of Colorado Denver, Aurora, CO, USA.
Plexiform neurofibroma (PN) is a leading cause of morbidity in children with the genetic condition Neurofibromatosis Type 1 (NF1), often disfiguring or threatening vital structures. During formation of PN, a complex tumor microenvironment (TME) develops, with recruitment of neoplastic and non-neoplastic cell types being critical for growth and progression. Due to the cohesive cellularity of PN, single-cell RNA-sequencing is difficult and may result in a loss of detection of critical cellular subpopulations.
View Article and Find Full Text PDFiScience
September 2023
Children's Brain Tumour Research Centre, University of Nottingham Biodiscovery Institute, Nottingham, UK.
Ependymoma (EPN) is a devastating childhood brain tumor. Single-cell analyses have illustrated the cellular heterogeneity of EPN tumors, identifying multiple neoplastic cell states including a mesenchymal-differentiated subpopulation which characterizes the PFA1 subtype. Here, we characterize the EPN immune environment, in the context of both tumor subtypes and tumor cell subpopulations using single-cell sequencing (scRNAseq, n = 27), deconvolution of bulk tumor gene expression (n = 299), spatial proteomics (n = 54), and single-cell cytokine release assays (n = 12).
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