Omics Investigations of Prostate Cancer Cells Exposed to Simulated Microgravity Conditions.

Abstract

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-µg) to serve as a model for metastasis and to derive transcriptional and epigenetic PC candidates from molecular biological changes. With an FDR of 10^-3, we detected the most differentially expressed genes in the two comparisons' adherent cells (AD) to MCSs (N = 751 genes) and 1g 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 SRMS gene in the 1g vs. AD comparison, as well as an additional 10,797 DMPs in the 1g vs. MCSs comparison. Finally, we identified five s-µg-related positive enrichments of transcription factor binding sites for AR, IRF1, IRF2, STAT1, STAT2, and FOXJ3 close to the DMPs.