Kirstein Anna, Schmid Thomas E, Combs Stephanie E
Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Department of Radiation Oncology, Technical University of Munich (TUM), Klinikum Rechts der Isar, 81675 Munich, Germany.
Cancers (Basel). 2020 Apr 28;12(5):1099. doi: 10.3390/cancers12051099.
Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O-methylguanine-DNA methyltransferase (MGMT) is nowadays routinely analyzed since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.
多形性胶质母细胞瘤（GBM）是成人中最常见的高级别颅内肿瘤。其特征在于不受控制的增殖、由于高侵袭性和迁移能力导致的弥漫性浸润，以及对化疗和放疗的强烈抗性。GBM的五年生存率低于3%，诊断后的平均生存率为12个月，因此GBM已成为当前研究的重点，迫切需要开发新的治疗方法以延长GBM患者的生存期。目前常规分析O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子区域的甲基化状态，因为甲基化的启动子区域有利于对基于替莫唑胺的化疗产生有效反应。此外，除了启动子甲基化外，还鉴定出几种通过在蛋白质翻译前降解MGMT mRNA来调节MGMT表达的微小RNA（miRNA）。这些miRNA可能是一种有前景的创新治疗方法，可增强MGMT未甲基化患者对替莫唑胺（TMZ）的敏感性，并提高无进展生存期以及长期生存率。在本综述中，对相关的miRNA进行了系统综述。
