Forensic Science Program, Physical Sciences Department, Alabama State University, Montgomery, AL, USA.
Physical Sciences Department, Alabama State University, Montgomery, AL, USA.
Gene. 2018 Oct 30;675:191-196. doi: 10.1016/j.gene.2018.06.090. Epub 2018 Jul 3.
The prostate gland is one of the last internal organs to deteriorate during human decomposition; however, this phenomenon is still mysterious. Gene expression in antemortem cases has been widely studied and a majority of the analyses concentrate on discovering basic physiological processes. The question of "What happens to gene expression after a human dies?" is a novel and emerging topic. Thanatotranscriptome (thanatos-, Greek for death) involves research on mRNA transcript abundances and gene expression in human tissues after death. Our previous studies have shown that RNA is a suitable and stable molecule in postmortem liver samples up to two days. Consequently, we hypothesized that there are also measurable and significant differences in mRNA transcript abundances in prostate tissues from human remains. In the current study, the goal was to identify apoptotic molecular markers (i.e., pro- and/or anti-apoptosis genes) that provide accurate gene expression profiles regarding the time of death. Tissue samples were removed by a medical examiner from the prostate of five cadavers during autopsy. After RNA extraction, cDNA was synthesized and the concentration was determined. The cDNA was reacted in apoptosis-related gene expression profiling by human PCR Array. The PCR Array results showed that at 38 h after death, a majority of the genes for apoptosis induction and positive regulation (i.e., caspases) were over-expressed more than at five days. The expression of anti-apoptotic genes such as BAG1, BCL2, and negative regulator of apoptosis, XIAP, was significantly elevated in a time-dependent manner. However, pro-apoptotic gene expression such as TP53 and TNFSF10 was not significantly upregulated. Therefore, postmortem prostate cells counteract programmed cell death with its anti-apoptotic machinery; yet as time progresses, pro-apoptotic mechanisms dominate. In conclusion, our study implies that over-expression of genes in male reproductive organs still occurs during decomposition, which may play substantial roles in forensic research and clinical application. These findings demonstrate that there is still active postmortem gene expression; however, our future research question will be, "When does gene expression terminate after death?"
前列腺是人类死后最后一个恶化的内部器官之一；然而，这种现象仍然很神秘。在生前病例中，基因表达已经得到了广泛的研究，大多数分析都集中在发现基本的生理过程上。“人死后基因表达会发生什么？”这个问题是一个新颖而新兴的话题。尸基因转录组（thanatos-，希腊语表示死亡）涉及死后人类组织中 mRNA 转录物丰度和基因表达的研究。我们之前的研究表明，在死后两天内，肝脏样本中的 RNA 是一种合适且稳定的分子。因此，我们假设在人体遗骸的前列腺组织中也存在可测量和显著的 mRNA 转录物丰度差异。在本研究中，我们的目标是确定凋亡分子标志物（即促凋亡和/或抗凋亡基因），以提供有关死亡时间的准确基因表达谱。尸检时，法医从五具尸体的前列腺中取出组织样本。提取 RNA 后，合成 cDNA 并确定浓度。cDNA 用于人类 PCR 阵列进行与凋亡相关的基因表达谱反应。PCR 阵列结果表明，死后 38 小时，大多数诱导凋亡和正向调节的基因（即半胱天冬酶）的表达比五天后明显增加。凋亡抑制基因如 BAG1、BCL2 和凋亡的负调节因子 XIAP 的表达呈时间依赖性显著升高。然而，促凋亡基因如 TP53 和 TNFSF10 的表达并没有明显上调。因此，死后前列腺细胞通过其抗凋亡机制来对抗程序性细胞死亡；然而，随着时间的推移，促凋亡机制占主导地位。总之，我们的研究表明，在分解过程中，男性生殖器官中的基因仍过度表达，这可能在法医学研究和临床应用中发挥重要作用。这些发现表明，死后仍存在活跃的基因表达；然而，我们未来的研究问题将是，“人死后基因表达何时终止？”
