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輔仁醫學期刊

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篇名 Glioblastoma Multiforme: The Role of MicroRNA in MGMT Expression Regulation
卷期 15:2
並列篇名 膠質母細胞瘤:小分子核糖核酸對甲基鳥嘌呤甲基轉移酶表現的調控作用
作者 謝政達黃紀榕田履黛
頁次 109-120
關鍵字 microRNAO6-methylguanine-DNA methyltransferaseGlioblastoma multiformeTemozolomide小分子核糖核酸甲基鳥嘌呤甲基轉移酶膠質母細胞瘤替莫唑胺
出刊日期 201706
DOI 10.3966/181020932017061502006

中文摘要

膠質母細胞瘤是最常見及最具侵略性的原發性中樞神經系統腫瘤,預後差。手術治療並搭配放療和化療是目前治療膠質母細胞瘤的標準模式。替莫唑胺,是一種新開發烷基化的化療藥物,被確認對這類患者的治療具有助長生命延長的效果。其中,膠質母細胞瘤細胞甲基鳥嘌呤甲基轉移酶蛋白質的表現,會干擾替莫唑胺所誘導的細胞毒性,導致替莫唑胺治療失敗。先前的研究發現甲基鳥嘌呤甲基轉移酶啟動子基因的甲基化現象,可以用來預測其蛋白質的表現,以解決利用免疫組織化學染色識別甲基鳥嘌呤甲基轉移酶蛋白表現的困難處。然而,甲基鳥嘌呤甲基轉移酶啟動子基因的甲基化狀態和蛋白質表現的不一致結果,發現小分子核糖核酸可能在轉錄後的調控,具有重要的作用,但此機轉尚不清楚。因此,這篇報告中整理在膠質母細胞瘤細胞株及檢體研究報告上,有關小分子核糖核酸對甲基鳥嘌呤甲基轉移酶表現的調控作用,以釐清甲基鳥嘌呤甲基轉移酶蛋白質的表現對替莫唑胺對膠質母細胞瘤治療效果的影響。

英文摘要

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system tumor with the worse prognosis. Surgical intervention following radiotherapy and chemotherapy is the standard treatment modality for GBM patients. Temozolomide (TMZ), a newly developed alkylating agent, is an effective chemoagent and confirmed to be benefit for patients survival. O6-methylguanine-DNA methyltransferase (MGMT) protein expression confers the TMZ-induced cytotoxicity, which lead to failure of TMZ therapy. Previously, the methylation of MGMT promoter gene is developed to predict the expression of MGMT protein because of the difficult identification in immunohistochemical staining. However, the MGMT expression between protein and methylation status of promoter gene is discordant, and microRNA is discovered to play an important role in the post-transcriptional regulation. Therefore, we summarize the exact roles of microRNA in the regulation of MGMT expression in GBM cell lines or tissue samples from the literatures, which may provide the further clinical application including prognosis prediction, chemo-sensitivity or therapeutic treatment.

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