Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China.
Institute of Cancer, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Environ Toxicol Pharmacol. 2019 May;68:141-147. doi: 10.1016/j.etap.2019.03.014. Epub 2019 Mar 15.
Increasing evidence showed that Cadmium (Cd) can accumulate in the body and damage cells, resulting in cancerigenesis of the prostate with complex mechanisms. In the present study, we aimed to explore the possible key genes, pathways and therapeutic drugs using bioinformatics methods. Microarray-based data were retrieved and analyzed to screen differentially expressed genes (DEGs) between Cd-treated prostate cells and controls. Then, functions of the DEGs were annotated and hub genes were screened. Next, key genes were selected from the hub genes via validation in a prostate cancer cohort from The Cancer Genome Atlas (TCGA). Afterward, potential drugs were further predicted. Consequently, a gene expression profile, GSE9951, was retrieved. Then, 361 up-regulated and 30 down-regulated DEGs were screened out, which were enriched in various pathways. Among the DEGs, seven hub genes (HSPA5, HSP90AB1, RHOA, HSPD1, MAD2L1, SKP2, and CCT2) were dysregulated in prostate cancer compared to normal controls, and two of them (HSPD1 and CCT2) might influence the prostate cancer prognosis. Lastly, ionomycin was predicted to be a potential agent reversing Cd-induced prostate cell malignant transformation. In summary, the present study provided novel evidence regarding the mechanisms of Cd-induced prostate cell malignant transformation, and identified ionomycin as a potential small molecule against Cd toxicity.
越来越多的证据表明,镉 (Cd) 可以在体内积累并损害细胞,导致前列腺发生癌症,其机制复杂。在本研究中,我们旨在使用生物信息学方法探索可能的关键基因、途径和治疗药物。我们检索并分析了基于微阵列的数据,以筛选 Cd 处理的前列腺细胞与对照之间差异表达的基因 (DEGs)。然后,注释 DEGs 的功能并筛选枢纽基因。接下来,我们从枢纽基因中选择关键基因,通过来自癌症基因组图谱 (TCGA) 的前列腺癌队列进行验证。之后,进一步预测潜在药物。结果,我们获得了一个基因表达谱,GSE9951。然后,筛选出 361 个上调和 30 个下调的 DEGs,它们富集在各种途径中。在 DEGs 中,与正常对照相比,七种枢纽基因(HSPA5、HSP90AB1、RHOA、HSPD1、MAD2L1、SKP2 和 CCT2)在前列腺癌中失调,其中两种(HSPD1 和 CCT2)可能影响前列腺癌的预后。最后,预测离子霉素可能是一种逆转 Cd 诱导的前列腺细胞恶性转化的潜在药物。总之,本研究为 Cd 诱导的前列腺细胞恶性转化的机制提供了新的证据,并确定离子霉素是一种对抗 Cd 毒性的潜在小分子药物。