OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer.
OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer.
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DOI：
10.1158/0008-5472.can-16-0359
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发表时间：
2016-07-01
期刊：
影响因子：
11.2
通讯作者：
Slack FJ
中科院分区：
文献类型：
--
作者：
Svoronos AA;Engelman DM;Slack FJ
microRNA是短的非编码RNA，其失调与大多数（如果不是全部）癌症有关。它们通过抑制mRNA翻译和降低mRNA稳定性来调节基因表达。为此，人们对修饰miRNA表达水平以治疗癌症非常感兴趣。然而，关于各种miRNA是致癌的还是肿瘤抑制的，文献充满了不一致的描述。在这篇评论中，我们直接研究这些不一致，并提出了几种机制来解释它们。这些机制包括特异性miRNA可以通过分别抑制肿瘤抑制mRNA和致癌mRNA同时产生竞争性致癌和肿瘤抑制作用的可能性。此外，miRNA可以调节肿瘤修饰的外在因素，如癌症-免疫系统相互作用、基质细胞相互作用、肿瘤病毒和对治疗的敏感性。最终，这些过程之间的平衡决定了特定的miRNA是否产生净致癌或净肿瘤抑制作用。对这一现象的深入理解可能会在评估癌症治疗的miRNA靶点方面证明是有价值的。
MicroRNAs are short, noncoding RNAs whose dysregulation has been implicated in most, if not all, cancers. They regulate gene expression by suppressing mRNA translation and reducing mRNA stability. To this end, there is a great deal of interest in modifying miRNA expression levels for the treatment of cancer. However, the literature is fraught with inconsistent accounts as to whether various miRNAs are oncogenic or tumor suppressive. In this review, we directly examine these inconsistencies and propose several mechanisms to explain them. These mechanisms include the possibility that specific miRNAs can simultaneously produce competing oncogenic and tumor suppressive effects by suppressing both tumor suppressive mRNAs and oncogenic mRNAs, respectively. In addition, miRNAs can modulate tumor-modifying extrinsic factors, such as cancer-immune system interactions, stromal cell interactions, oncoviruses, and sensitivity to therapy. Ultimately, it is the balance between these processes which determines whether a specific miRNA produces a net oncogenic or net tumor suppressive effect. A solid understanding of this phenomenon will likely prove valuable in evaluating miRNA targets for cancer therapy.