Neuroscience Laboratory, Health Sciences Institute, Bahcesehir University, Istanbul, Turkey.
Department of Neurosurgery, Bahcesehir University School of Medicine, Istanbul, Turkey.
J Cell Mol Med. 2023 Sep;27(17):2603-2613. doi: 10.1111/jcmm.17883. Epub 2023 Jul 31.
Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed. Cell death was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived glioma cells concerning IDH1 mutation and WHO grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted proliferation in glioma cells. MEG3 inhibition improved the chemosensitivity of glioma cells to 5-fluorouracil (5FU) but not to navitoclax. On the other hand, there is no significant effect of MEG3 expression on temozolamide (TMZ) treatment which is a standard chemotherapeutic agent in glioma. Suppression of the MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemosensitivity were not affected by MEG3 inhibition. Further, as a possible cell death mechanism of action apoptosis was investigated. Although MEG3 is a widely known tumour suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used for improving the efficiency of known chemotherapeutic drug sensitivity. We propose that the level of MEG3 should be evaluated in the treatment of different glioma subtypes that are resistant to effective drugs to increase the potential effective drug applications.
异常表达的 MEG3 已在多种癌症中被发现。本研究旨在通过调节 MEG3 的表达来评估 MEG3 对神经胶质瘤细胞的影响，并利用潜在的化疗药物治疗神经胶质瘤。测定细胞活力、迁移和化疗敏感性。评估 MEG3 过表达和 MEG3 抑制细胞中的细胞死亡。比较 IDH1 突变和 WHO 分级的患者来源的神经胶质瘤细胞中的 MEG3 表达。沉默 MEG3 抑制神经胶质瘤细胞的增殖并减少细胞迁移，而 MEG3 过表达则促进神经胶质瘤细胞的增殖。MEG3 抑制提高了神经胶质瘤细胞对 5-氟尿嘧啶（5FU）的化疗敏感性，但对 navitoclax 没有影响。另一方面，MEG3 表达对替莫唑胺（TMZ）治疗没有显著影响，TMZ 是神经胶质瘤的标准化疗药物。在患者来源的少突胶质细胞瘤细胞中抑制 MEG3 基因也显示出相同的效果，而神经母细胞瘤细胞的增殖和化疗敏感性不受 MEG3 抑制的影响。此外，作为一种可能的细胞死亡机制，研究了细胞凋亡。虽然 MEG3 是一种广泛知晓的肿瘤抑制基因，其缺失与多种癌症类型有关，但在这里我们报告说，抑制 MEG3 可以提高已知化疗药物敏感性的效率。我们建议，在治疗对有效药物耐药的不同神经胶质瘤亚型时，应评估 MEG3 的水平，以增加潜在有效药物的应用。
