Center for Systems Biology, Soochow University, Suzhou, China.
School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou, China.
Brief Bioinform. 2020 Mar 23;21(2):441-457. doi: 10.1093/bib/bbz006.
Crosstalk between competing endogenous RNAs (ceRNAs) is mediated by shared microRNAs (miRNAs) and plays important roles both in normal physiology and tumorigenesis; thus, it is attractive for systems-level decoding of gene regulation. As ceRNA networks link the function of miRNAs with that of transcripts sharing the same miRNA response elements (MREs), e.g. pseudogenes, competing mRNAs, long non-coding RNAs, and circular RNAs, the perturbation of crucial interactions in ceRNA networks may contribute to carcinogenesis by affecting the balance of cellular regulatory system. Therefore, discovering biomarkers that indicate cancer initiation, development, and/or therapeutic responses via reconstructing and analyzing ceRNA networks is of clinical significance. In this review, the regulatory function of ceRNAs in cancer and crucial determinants of ceRNA crosstalk are firstly discussed to gain a global understanding of ceRNA-mediated carcinogenesis. Then, computational and experimental approaches for ceRNA network reconstruction and ceRNA validation, respectively, are described from a systems biology perspective. We focus on strategies for biomarker identification based on analyzing ceRNA networks and highlight the translational applications of ceRNA biomarkers for cancer management. This article will shed light on the significance of miRNA-mediated ceRNA interactions and provide important clues for discovering ceRNA network-based biomarker in cancer biology, thereby accelerating the pace of precision medicine and healthcare for cancer patients.
竞争性内源性 RNA（ceRNA）之间的串扰受共享 microRNAs（miRNAs）介导，并在正常生理和肿瘤发生中发挥重要作用；因此，它是系统解码基因调控的有吸引力的目标。由于 ceRNA 网络将 miRNA 的功能与具有相同 miRNA 反应元件（MRE）的转录本的功能联系起来，例如假基因、竞争 mRNA、长非编码 RNA 和环状 RNA，ceRNA 网络中关键相互作用的扰动可能通过影响细胞调节系统的平衡而导致癌变。因此，通过重建和分析 ceRNA 网络发现指示癌症起始、发展和/或治疗反应的生物标志物具有临床意义。在这篇综述中，首先讨论了 ceRNA 在癌症中的调节功能和 ceRNA 串扰的关键决定因素，以全面了解 ceRNA 介导的致癌作用。然后，从系统生物学的角度分别描述了 ceRNA 网络重建和 ceRNA 验证的计算和实验方法。我们专注于基于分析 ceRNA 网络进行生物标志物识别的策略，并强调 ceRNA 生物标志物在癌症管理中的转化应用。本文将阐明 miRNA 介导的 ceRNA 相互作用的意义，并为发现癌症生物学中的 ceRNA 网络生物标志物提供重要线索，从而加速癌症患者的精准医疗和医疗保健步伐。
