PDF(Pubmed)
Abstract：
Vitamin D3 is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D3 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 D3 metabolite, 1α,25(OH)2D3, at 24 h. Differential gene expression analysis revealed 1601 significant genes affected by 1α,25(OH)2D3 treatment. Pathway enrichment analysis predicted 1α,25(OH)2D3- mediated repression of prostate cancer, cell proliferation, actin cytoskeletal, and actin-related signaling pathways (p < 0.05). Prioritizing genes with vitamin D response elements and associating expression levels with overall survival (OS) in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) cohort, we identified ANLN (Anillin) and ECT2 (Epithelial Cell Transforming 2) as potential prognostic PCa biomarkers. Both genes were strongly correlated and significantly downregulated by 1α,25(OH)2D3 treatment, where low expression was statistically associated with better overall survival outcomes in the TCGA PRAD public cohort. Increased ANLN and ECT2 mRNA gene expression was significantly associated with PCa, and Gleason scores using both the TCGA cohort (p < 0.05) and an AA non-malignant/tumor-matched cohort. Our findings suggest 1α,25(OH)2D3 regulation of these biomarkers may be significant for PCa prevention. In addition, 1α,25(OH)2D3 could be used as an adjuvant treatment targeting actin cytoskeleton signaling and actin cytoskeleton-related signaling pathways, particularly among AA men.
摘要：
维生素D3是一种类固醇激素，可在前列腺细胞中赋予抗肿瘤特性。血清维生素D3缺乏与晚期前列腺癌（PCa）有关，特别影响非裔美国人（AA）男性。因此,阐明维生素D对信号通路的多效性作用，对维持非恶性肿瘤至关重要，可能会提供额外的药物靶标，以减轻PCa男性的不同结果，尤其是AA男性。我们对AA非恶性前列腺细胞系进行了RNA测序，RC-77N/E,将未经处理的细胞与用10nM维生素D3代谢物处理的细胞进行比较，1α,25（OH）2D3，在24小时。差异基因表达分析显示1601个显著基因受1α，25（OH）2D3处置。途径富集分析预测1α，25（OH）2D3-介导的前列腺癌抑制，细胞增殖，肌动蛋白细胞骨架，和肌动蛋白相关信号通路(p<0.05)。在癌症基因组图谱前列腺癌（TCGAPRAD）队列中，优先考虑具有维生素D反应元件的基因并将表达水平与总生存期（OS）相关联，我们确定ANLN(Anillin)和ECT2(上皮细胞转化2)为潜在的PCa预后生物标志物.这两个基因强烈相关，并显著下调1α，25（OH）2D3处理，在TCGAPRAD公共队列中,低表达与更好的总体生存结局具有统计学相关性.ANLN和ECT2mRNA基因表达增加与PCa显著相关,和使用TCGA队列(p<0.05)和AA非恶性肿瘤/肿瘤匹配队列的Gleason评分。我们的研究结果表明1α，25（OH）2D3对这些生物标志物的调节可能对预防PCa具有重要意义。此外,1α,25(OH)2D3可作为靶向肌动蛋白细胞骨架信号和肌动蛋白细胞骨架相关信号通路的辅助治疗,尤其是AA男性。
