Department of Biological Sciences, Laboratório de Biologia Molecular do Câncer, UNIFESP, Universidade Federal de São Paulo, Campus Diadema, São Paulo 04039‑032, Brazil.
Department of Biochemistry, Insitute of Pharmacology, Universidade Federal de São Paulo, Campus São Paulo, São Paulo 04044‑020, Brazil.
Mol Med Rep. 2019 Jun;19(6):5023-5029. doi: 10.3892/mmr.2019.10142. Epub 2019 Apr 9.
Multiple myeloma (MM) is an incurable disease; a better understanding of the molecular aspects of this hematological malignancy could contribute to the development of new treatment strategies and help to improve the survival rates of patients with MM. Previously, the methylation status of the deleted in colorectal cancer (DCC) gene was correlated with the survival rate of patients with MM, thus the main goal of this study was to understand DCC contribution to MM tumorigenesis, and to assess the impact of DCC inhibition in the MM response to treatment with bortezomib. Our results demonstrated that hypermethylation of the DCC promoter inhibits gene expression, and DCC silencing is significantly correlated with a reduction in cell viability and an increase in cell death induced by bortezomib. In conclusion, our results suggested that hypermethylation is an important mechanism of DCC expression regulation in MM and that the absence of DCC contributes to the enhanced sensitivity to treatment with bortezomib.
多发性骨髓瘤（MM）是一种无法治愈的疾病；更好地了解这种血液恶性肿瘤的分子方面，可能有助于开发新的治疗策略，并有助于提高 MM 患者的生存率。此前，结直肠癌缺失基因（DCC）的甲基化状态与 MM 患者的生存率相关，因此本研究的主要目的是了解 DCC 对 MM 肿瘤发生的贡献，并评估 DCC 抑制对 MM 对硼替佐米治疗反应的影响。我们的结果表明，DCC 启动子的高甲基化抑制基因表达，DCC 沉默与硼替佐米诱导的细胞活力降低和细胞死亡增加显著相关。总之，我们的结果表明，甲基化是 MM 中 DCC 表达调控的一个重要机制，而 DCC 的缺失有助于增强对硼替佐米治疗的敏感性。
