Ergun Sercan, Oztuzcu Serdar
Ulubey Vocational Higher School, Ordu University, Ordu, Turkey,
Tumour Biol. 2015 May;36(5):3129-36. doi: 10.1007/s13277-015-3346-x. Epub 2015 Mar 27.
Competing endogenous RNAs (ceRNAs) are RNA transcripts which can communicate with each other by decreasing targeting concentration of micro-RNA (miRNA) with the derepression of other messenger RNAs (mRNAs) having the common miRNA response elements (MREs). Oncocers are ceRNAs taking crucial roles in oncogenic pathways processed in many types of cancer, and this study analyzes oncocer-mediated cross-talk by sponging microRNAs (miRNAs) in these pathways. While doing this, breast, liver, colon, prostate, gastric, lung, endometrium, thyroid and epithelial cancers and melanoma, rhabdomyosarcoma, glioblastoma, acute promyelocytic leukemia, retinoblastoma, and neuroblastoma were analyzed with respect to ceRNA-based carcinogenesis. This study defines, firstly, oncocers in the literature and contains all oncocer-related findings found up to now. Therefore, it will help to increase our comprehension about oncocer-mediated mechanisms. Via this study, a novel perspective would be produced to make clear cancer mechanisms and suggest novel approaches to regulate ceRNA networks via miRNA competition for cancer therapeutics. Graphical Abstract Multiple RNA transcripts have common MREs for the similar miRNA in their 3'-untranslated regions (3'-UTRs). Upregulation of ceRNAs rises the abundance of specific MREs and shifts the miRNA pool distribution, as a result, leading to the increased expression of target mRNA. The depot of genomic mutations and epigenetic alterations changing gene function and expression causes cancers. Herewith, genome-based somatic base-pair mutations, DNA copy number alterations, chromosomal translocation, also transcript fusions, alternative splicing are usually seen in cancer situations. Consequently, such cases causing changed UTR expression in transcripts influence the levels of MRE or present new MREs into the cells. Alterations in MREs of ceRNAs affect the capability of a specific mRNA transcript to attach or titrate miRNAs. As a result, the disturbed ceRNA network can lead to diseases and cancers. As a new term in RNA world, oncocers-the name for ceRNAs taking crucial roles in oncogenic pathways-are processed in many types of cancer, and oncocer-mediated cross-talk are analyzed by sponging miRNAs in these pathways.
竞争性内源性RNA（ceRNA）是一类RNA转录本，它们可以通过解除对具有共同微小RNA反应元件（MRE）的其他信使RNA（mRNA）的抑制，降低微小RNA（miRNA）的靶向浓度，从而实现相互通讯。癌源RNA是ceRNA的一种，在多种癌症发生的致癌途径中发挥关键作用，本研究通过在这些途径中竞争性结合微小RNA（miRNA）来分析癌源RNA介导的相互作用。在此过程中，研究人员针对基于ceRNA的致癌作用，对乳腺癌、肝癌、结肠癌、前列腺癌、胃癌、肺癌、子宫内膜癌、甲状腺癌、上皮癌以及黑色素瘤、横纹肌肉瘤、胶质母细胞瘤、急性早幼粒细胞白血病、视网膜母细胞瘤和神经母细胞瘤进行了分析。本研究首先对文献中的癌源RNA进行了定义，并涵盖了截至目前所有与癌源RNA相关的研究发现。因此，这将有助于增进我们对癌源RNA介导机制的理解。通过本研究，有望产生一个全新的视角，以阐明癌症机制，并通过miRNA竞争调节ceRNA网络，为癌症治疗提供新的方法。
图形摘要：多个RNA转录本在其3'非翻译区（3'-UTR）具有针对相似miRNA的共同MRE。ceRNA的上调增加了特定MRE的丰度，改变了miRNA库的分布，从而导致靶mRNA的表达增加。基因组突变和表观遗传改变的累积会改变基因功能和表达，进而引发癌症。因此，基于基因组的体细胞碱基对突变、DNA拷贝数改变、染色体易位以及转录本融合、可变剪接等情况在癌症中较为常见。这些情况会导致转录本中UTR表达的改变，影响MRE的水平或在细胞中产生新的MRE。ceRNA的MRE改变会影响特定mRNA转录本结合或滴定miRNA的能力。结果，ceRNA网络的紊乱可能导致疾病和癌症。作为RNA世界中的一个新术语，癌源RNA（即在致癌途径中发挥关键作用的ceRNA）在多种癌症中都有涉及，本研究通过在这些途径中竞争性结合miRNA来分析癌源RNA介导的相互作用。
