Division of Oncology, Department of Surgery and Cancer, Imperial Centre for Translational and Experimental Medicine, Imperial College, London, United Kingdom.
Mol Cell Biol. 2013 Oct;33(20):3976-82. doi: 10.1128/MCB.00683-13. Epub 2013 Aug 5.
The capacity of noncoding RNA to regulate gene expression in health and disease is epitomized by the microRNAs, small ∼22-nucleotide RNAs that target mRNAs to repress their translation into protein. Recently a previously unrecognized gene regulatory layer has emerged, characterized by the ability of a wide range of RNA transcripts to vie for microRNA binding and alleviate the repressive effect of microRNAs on their mRNA targets. Termed competing endogenous RNAs (ceRNAs), these participate in a microRNA-dependent cross talk, producing robust networks that when perturbed may lead to cancer. To date, the tumor suppressor PTEN has been most extensively validated as competing with a variety of ceRNAs in different cancers: reducing these ceRNAs appears to reduce PTEN levels, tipping cells toward cancer progression. In this review we look at ceRNA networks in cancer, their characteristics, and constituent parts, focusing on the insights that can be gained from the studies conducted on PTEN. We also explore the conditions that facilitate ceRNA cross talk, proposing that the disruption of these conditions may represent a general phenomenon in carcinogenesis.
非编码 RNA 调控健康和疾病中基因表达的能力，以 microRNAs 为代表，microRNAs 是一种大约 22 个核苷酸的小分子 RNA，能够靶向 mRNAs 并抑制其翻译成蛋白质。最近，出现了一个以前未被认识到的基因调控层，其特征是广泛的 RNA 转录本能够争夺 microRNA 结合并减轻 microRNA 对其 mRNA 靶标的抑制作用。这些 RNA 被称为竞争性内源 RNA（ceRNA），它们参与 microRNA 依赖的串扰，形成强大的网络，这些网络受到干扰可能导致癌症。迄今为止，肿瘤抑制因子 PTEN 被最广泛地验证为与不同癌症中的多种 ceRNA 竞争：降低这些 ceRNA 的水平似乎会降低 PTEN 水平，使细胞向癌症进展倾斜。在这篇综述中，我们研究了 ceRNA 网络在癌症中的作用、特征和组成部分，重点关注了从 PTEN 研究中获得的见解。我们还探讨了促进 ceRNA 串扰的条件，提出破坏这些条件可能是致癌发生的一个普遍现象。
