Causes and consequences of microRNA dysregulation.
Causes and consequences of microRNA dysregulation.
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DOI：
10.1097/ppo.0b013e318250c001
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Croce CM
中科院分区：
文献类型：
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作者：
Iorio MV;Croce CM
目前人们普遍认识到，microRNA 失调是人类癌症的一个标志，这些微小调节 RNA 分子在多种细胞类型中的异常表达不仅仅是随机关联，而且在肿瘤发生过程的不同步骤中发挥着因果作用，从起始和发展到获得转移表型的进展。不同的调控机制可以在遗传或表观遗传水平上控制 microRNA 表达，并涉及生物发生机制或特定转录因子的招募。致瘤过程意味着这些机制的实质性改变，从而破坏细胞内的平衡并导致 microRNA 表达的整体变化，导致抑癌 microRNA 的丧失和 oncomiRNA 的过度表达。在这里，我们回顾了调节 microRNA 的主要机制，以及它们在癌症中异常表达的后果，并从临床角度看一下可能的影响。
It is currently well recognized that microRNA deregulation is an hallmark of human cancer, and how an aberrant expression of these tiny regulatory RNA molecules in several cell types is not just a random association, but it plays a causal role in different steps of the tumorigenic process, from the initiation and development to progression toward the acquisition of a metastatic phenotype. Different regulatory mechanisms can control microRNA expression at a genetic or epigenetic level as well as involving the biogenesis machinery or the recruitment of specific transcription factors. The tumorigenic process implies a substantial alteration of these mechanisms, thus disrupting the equilibrium within the cell and leading to a global change in microRNA expression, with loss of oncosuppressor microRNAs and overexpression of oncomiRNAs. Here we review the main mechanisms regulating microRNAs, and the consequences of their aberrant expression in cancer, with a glance at the possible implications at a clinical point of view.