研究动态
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MEG3基因的沉默促进了胶质瘤中的抗癌活性和药物敏感性。

Silencing of the MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma.

发表日期:2023 Jul 31
作者: Zehra Degirmenci, Sena Unver, Turker Kilic, Timucin Avsar
来源: Cell Death & Disease

摘要:

MEG3在各种癌症中的异常表达已被证明。本研究的目的是评估MEG3对胶质瘤细胞的影响,以及通过调节MEG3表达来使用潜在的化疗药物治疗胶质瘤。评估了细胞存活率、迁移和化疗敏感性。评估了MEG3过表达和MEG3抑制细胞的细胞死亡情况。比较了与IDH1突变和WHO分级相关的患者源性胶质瘤细胞中的MEG3表达。抑制MEG3可抑制细胞增殖并减少细胞迁移,而MEG3过表达则促进胶质瘤细胞的增殖。MEG3抑制改善了胶质瘤细胞对5-氟尿嘧啶(5-FU)的化疗敏感性,但对navitoclax的敏感性没有显著影响。另一方面,MEG3表达对于苯甲酰环腺苷(TMZ)治疗(胶质瘤的标准化疗药物)没有显著影响。在患者源性寡突胶质瘤细胞中抑制MEG3还显示出相同的效果,但MEG3抑制没有影响到胶质母细胞瘤细胞的增殖和化疗敏感性。此外,还对细胞凋亡作为潜在的细胞死亡机制进行了调查。尽管MEG3是众所周知的肿瘤抑制基因,其丧失与多种癌症类型相关,但我们在这里报告了MEG3抑制可用于提高已知化疗药物敏感性的效率。我们建议在对抗有效药物耐药的不同胶质母细胞瘤亚型的治疗中,评估MEG3的水平,以增加潜在的有效药物应用。©2023 The Authors. Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.出版的《细胞与分子医学杂志》
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.© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.