School of Management, Jilin University, Changchun, China.
Department of Urology, The First Hospital of Jilin University, Changchun, China.
DNA Cell Biol. 2020 May;39(5):836-847. doi: 10.1089/dna.2019.5247. Epub 2020 Feb 26.
Prostate cancer (PCa) is a common malignant tumor in elderly men worldwide. Most primary PCas inevitably progress into castration-resistant prostate cancer (CRPC) after androgen deprivation therapy. The mechanisms contributing to this progression are still controversial. In this study, functional module genes, DNA methylations, core regulators, and potential drugs in primary PCa and CRPC were explored by integrating a series of bioinformatics analyses. First, 588 differentially expressed genes (DEGs) were identified. Combined with related genes, protein-protein interaction networks were constructed, and 22 and 14 significant modules were identified in primary PCa and CRPC, respectively. More DEGs were identified in differentially methylated genes in CRPC modules. The hub genes in CRPC included and . Moreover, core noncoding RNAs and transcription factors that significantly regulate CRPC modules were identified, including , , , and . Finally, the prediction of potential drugs for primary PCa and CRPC was also performed. Exisulind and phosphodiesterase-4 inhibitors were predicted as potential drugs for CRPC. The results of this study provide a new way for biologists and pharmacists to understand the potential molecular mechanisms of CRPC and also provide valuable references for drug redirection and new drug development for PCa.
前列腺癌（PCa）是全球老年男性中常见的恶性肿瘤。大多数原发性 PCa 在雄激素剥夺治疗后不可避免地进展为去势抵抗性前列腺癌（CRPC）。导致这种进展的机制仍存在争议。在这项研究中，通过整合一系列生物信息学分析，探讨了原发性 PCa 和 CRPC 中的功能模块基因、DNA 甲基化、核心调控因子和潜在药物。首先，鉴定了 588 个差异表达基因（DEGs）。结合相关基因，构建蛋白质-蛋白质相互作用网络，分别在原发性 PCa 和 CRPC 中鉴定出 22 个和 14 个显著模块。CRPC 模块中差异甲基化基因的 DEGs 更多。CRPC 的枢纽基因包括 和 。此外，还鉴定了显著调控 CRPC 模块的核心非编码 RNA 和转录因子，包括 、 、 和 。最后，还对原发性 PCa 和 CRPC 的潜在药物进行了预测。预测 Exisulind 和磷酸二酯酶-4 抑制剂为 CRPC 的潜在药物。本研究为生物学家和药剂师提供了一种理解 CRPC 潜在分子机制的新方法，也为 PCa 的药物重定向和新药开发提供了有价值的参考。
