miRNA interventions serve as 'magic bullets' in the reversal of glioblastoma hallmarks.
miRNA interventions serve as 'magic bullets' in the reversal of glioblastoma hallmarks.
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DOI：
10.18632/oncotarget.5926
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发表时间：
2015-11-17
期刊：
影响因子：
--
通讯作者：
Kang C
中科院分区：
文献类型：
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作者：
Chen L;Kang C
microRNA（miRNAs）不再被认为是人类转录组中的小片段RNA“垃圾”，而是被认为是基因表达的主调节因子，其在维持转录后细胞稳态中至关重要。这一概念引发了人们对研究人类疾病，特别是癌症中miRNA失调的极大兴趣。胶质母细胞瘤（GBM）长期以来一直是成人CNS肿瘤的高死亡率和发病率的主要原因，这是缺乏逆转GBM的标志性特征（例如，无边界扩张和扩散渗透）。在过去的十年中，解剖GBM的分子结构，导致更好地理解的分子基础的标志，产生了许多有前途的药理学蛋白质的目标。然而，很少有临床反应被强调，这表明需要新的治疗策略和目标。本文系统地总结了在GBM标志物的发展中具有一个或多个功能靶点的上下文依赖性验证的miRNA，并回顾了当前的miRNA靶向策略。我们注意到，只有少数基于miRNA的治疗方法进行了临床意义的试验，并且没有一种是针对GBM的，因此敦促我们将miRNA治疗方法单独或联合应用于第一线。
microRNAs (miRNAs) are no longer deemed small pieces of RNA “trash” in the human transcriptome but are considered to be master regulators of gene expression that are critical in maintaining cellular homeostasis post-transcriptionally. The concept triggers great interest in studying miRNA dysregulations in human diseases, especially in cancers. Glioblastoma (GBM) has long been the leading cause of the high mortality and morbidity of CNS tumors in adults, which is a consequence of the lack of strategies to reverse the hallmark features of GBM (e.g., borderless expansion and diffuse infiltration). In the past decade, dissecting the molecular architecture of GBM has led to a better understanding of the molecular basis of the hallmarks, generating many promising pharmacological protein targets. However, few clinical responses have been highlighted, suggesting the demand for new therapeutic strategies and targets. In this review, we systemically summarize the context-dependently validated miRNAs with one or more functional targets in the development of GBM hallmarks and review the current miRNA-targeting strategies. We note that only a few miRNA-based therapeutics are trialed for clinical significance, and none of them is tailored to GBM, thereby urging us to bring miRNA therapeutics to the front line either alone or in combination.