1,25-Dihydroxyvitamin D[sub.3] Suppresses Prognostic Survival Biomarkers Associated with Cell Cycle and Actin Organization in a Non-Malignant African American Prostate Cell Line

Vitamin D[sub.3] is a steroid hormone that has been shown to prevent tumor growth in prostate cells. Not having enough vitamin D[sub.3] in the blood has been linked to advanced prostate cancer and mortality, especially in African American men. We wanted to understand how vitamin D affected pathways that keep prostate cells from becoming cancerous, which could lead to new therapeutic targets and treatments, especially for African American men who tend to be more prone to being vitamin D deficient compared to European men. Here, we studied a non-cancerous African American prostate cell line treated with the active form of vitamin D with a concentration similar to what is found in the body for 24 h. Using RNA whole-transcriptome sequencing, we compared these treated cells with untreated cells to assess genes and pathways significantly changed due to treatment. We found that vitamin D affected the activity of 1601 genes, mainly suppressing pathways linked to prostate cell movement, growth, and viability. Only two genes, ANLN and ECT2, were strongly correlated with prostate cancer prognosis and patients tended to have better survival rates when these genes were less active. Furthermore, downregulation of ANLN and ECT2 was also shown to repress signaling pathways involved in prostate cell movement, growth, malignant transformation, and viability. Our results suggest that vitamin D decreases the activity of these genes and could be important for preventing prostate cancer, especially for African American men. This could lead to the development of new treatments targeting specific genes and pathways involved in prostate cancer growth. Vitamin D[sub.3] is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D[sub.3] deficiency has been associated with advanced prostate cancer (PCa), particularly affecting African American (AA) men. Therefore, elucidating the pleiotropic effects of vitamin D on signaling pathways, essential to maintaining non-malignancy, may provide additional drug targets to mitigate disparate outcomes for men with PCa, especially AA men. We conducted RNA sequencing on an AA non-malignant prostate cell line, RC-77N/E, comparing untreated cells to those treated with 10 nM of vitamin D[sub.3] metabolite, 1α,25(OH)[sub.2]D[sub.3], at 24 h. Differential gene expression analysis revealed 1601 significant genes affected by 1α,25(OH)[sub.2]D[sub.3] treatment. Pathway enrichment analysis predicted 1α,25(OH)[sub.2]D[su