Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China.
DNA Cell Biol. 2013 Jun;32(6):292-7. doi: 10.1089/dna.2013.2042. Epub 2013 Apr 27.
DNA methylation plays an essential role in carcinogenesis. Promoter hypermethylation can result in transcriptional silencing of specific genes, such as tumor suppressors. Thus far, few reports have investigated the effect of curcumin, an active component of the perennial herb Curcuma longa, on DNA methylation. In the present study, we evaluated the effects of curcumin on receptor activator of NF-κB (RANK) gene expression in human glioblastoma cells. Incubation of cells with therapeutic concentrations of curcumin resulted in a significant elevation of RANK expression at both the mRNA and protein levels in two glioblastoma cell lines. We further confirmed that this elevation was associated with promoter demethylation through methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing PCR. Additionally, we demonstrated that knockdown of STAT3, an oncogenic transcription factor, is sufficient to induce RANK promoter demethylation along with RANK reactivation. These results demonstrated that curcumin induced RANK gene reactivation through epigenetic modification in human glioblastoma cells, and that STAT3 is involved in RANK promoter hypermethylation and epigenetic silencing, thus allowing for further applications of curcumin epigenetic therapy in glioma and therapeutic implications of STAT3 in human glioblastoma.
DNA 甲基化在致癌作用中起着至关重要的作用。启动子过度甲基化可导致特定基因（如肿瘤抑制基因）的转录沉默。迄今为止，很少有研究报道姜黄素（多年生草本植物姜黄的活性成分）对 DNA 甲基化的影响。在本研究中，我们评估了姜黄素对人神经胶质瘤细胞中核因子-κB（NF-κB）受体激活剂（RANK）基因表达的影响。用治疗浓度的姜黄素孵育细胞可导致两种神经胶质瘤细胞系的 RANK 表达在 mRNA 和蛋白质水平上均显著升高。我们进一步通过甲基化特异性聚合酶链反应（PCR）和亚硫酸氢盐测序 PCR 证实，这种升高与启动子去甲基化有关。此外，我们证明了致癌转录因子 STAT3 的敲低足以诱导 RANK 启动子去甲基化以及 RANK 重新激活。这些结果表明，姜黄素通过人神经胶质瘤细胞中的表观遗传修饰诱导 RANK 基因重新激活，并且 STAT3 参与 RANK 启动子过度甲基化和表观遗传沉默，从而允许姜黄素表观遗传疗法在神经胶质瘤中的进一步应用以及 STAT3 在人神经胶质瘤中的治疗意义。
