Schulz Herbert, Abdelfattah Fatima, Heinrich Anna, Melnik Daniela, Sandt Viviann, Krüger Marcus, Wehland Markus, Hoffmann Per, Cortés-Sánchez José Luis, Evert Matthias, Evert Katja, Grimm Daniela
Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, 39106 Magdeburg, Germany.
Research Group "Magdeburger Arbeitsgemeinschaft für Forschung unter Raumfahrt- und Schwerelosigkeitsbedingungen" (MARS), Otto von Guericke University, 39106 Magdeburg, Germany.
Biomolecules. 2025 Feb 18;15(2):303. doi: 10.3390/biom15020303.
Prostate cancer (PC) is the most diagnosed cancer in males across the globe. Following the formation of metastasis, PC is linked to a notable decline in both prognosis and survival rates. Three-dimensional multicellular spheroids (MCSs) of a prostate adenocarcinoma cell line were generated in a three-day simulated microgravity environment (s-µ) to serve as a model for metastasis and to derive transcriptional and epigenetic PC candidates from molecular biological changes. With an FDR of 10, we detected the most differentially expressed genes in the two comparisons' adherent cells (AD) to MCSs (N = 751 genes) and 1 control cells to MCSs (N = 662 genes). In these two comparisons, genes related to cell cycle, angiogenesis, cell adhesion, and extracellular space were consistently found to be significantly enriched in GO annotations. Furthermore, at a 5% FDR significance level, we were able to identify 11,090 genome-wide differentially methylated positions (DMPs) and one differentially methylated region in the gene in the 1 vs. AD comparison, as well as an additional 10,797 DMPs in the 1 vs. MCSs comparison. Finally, we identified five s-µ-related positive enrichments of transcription factor binding sites for AR, IRF1, IRF2, STAT1, STAT2, and FOXJ3 close to the DMPs.
前列腺癌(PC)是全球男性中诊断出最多的癌症。在发生转移后,PC与预后和生存率的显著下降有关。在为期三天的模拟微重力环境(s-µ)中生成了前列腺腺癌细胞系的三维多细胞球体(MCSs),以作为转移模型,并从分子生物学变化中推导转录和表观遗传的PC候选物。在错误发现率(FDR)为10的情况下,我们在贴壁细胞(AD)与MCSs的两次比较(N = 751个基因)以及1个对照细胞与MCSs的比较(N = 662个基因)中检测到了差异表达最显著的基因。在这两次比较中,始终发现与细胞周期、血管生成、细胞粘附和细胞外空间相关的基因在基因本体(GO)注释中显著富集。此外,在5%的FDR显著性水平下,我们能够在1与AD的比较中鉴定出全基因组范围内11,090个差异甲基化位点(DMPs)以及该基因中的一个差异甲基化区域,在1与MCSs的比较中还鉴定出另外10,797个DMPs。最后,我们在靠近DMPs的位置鉴定出与AR、IRF1、IRF2、STAT1、STAT2和FOXJ3相关的五个与s-µ相关的转录因子结合位点的正富集。