Abstract—

It was more than twenty years ago that miRNAs were recognized as a new class of RNA, but the understanding of their regulatory role is just beginning to emerge. Furthermore, it was found that the function of miRNAs as “master regulators” can be controlled by other non-coding RNAs (ncRNAs), in particular, long ncRNAs (lncRNAs). The regulatory functions of lncRNAs have been indicated in tumors in various locations and, in particular, in osteosarcoma, the most common and most aggressive malignant bone disease in children during puberty. This review discusses studies about the role of lncRNAs in the regulation of gene expression by the competitive endogenous RNAs (ceRNAs) mechanism. Data from these publications confirm the involvement of lncRNAs in the major signaling pathways, such as Notch, PI3K/AKT, Wnt/β-catenin, JNK, and HIV/VEGF. For example, seven members of the SNHG family (small nucleolar RNA host gene) were shown to participate in the Notch and PI3K/AKT signaling pathways; moreover, several lncRNA/miRNA/mRNA regulatory axes were identified for nearly all members of this family. The functions of other multifunctional oncogenic lncRNAs are also discussed; in particular, six to ten such axes have been determined for TUG1, MALAT1, and XIST. Using the Gene Cards, KEGG, and Panther databases, the key signaling pathways were identified for the targets of these three multifunctional lncRNAs. Investigation of lncRNA function contributes to the development of new diagnostic and prognostic markers for the treatment of patients with osteosarcoma. According to the available data, interactions between ceRNAs, that is, miRNAs, mRNAs, and lncRNAs, represent a new form of gene expression regulation that is involved in various pathophysiological processes, including bone oncogenesis.

中文翻译：

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长的非编码RNA作为骨肉瘤中的竞争性内源RNA

摘要-

二十多年前，miRNA被公认为是一类新型的RNA，但对其调节作用的了解才刚刚开始。此外，发现miRNA作为“主调节剂”的功能可以受其他非编码RNA（ncRNA），特别是长ncRNA（lncRNA）的控制。lncRNA的调节功能已在各个部位的肿瘤中得到了证实，尤其是在骨肉瘤中，这是青春期儿童中最常见，最具侵袭性的恶性骨病。这篇综述讨论了有关lncRNA在竞争性内源RNA（ceRNA）机制调控基因表达中的作用的研究。这些出版物的数据证实lncRNA参与了主要的信号通路，例如Notch，PI3K / AKT，Wnt /β-catenin，JNK和HIV / VEGF。例如，显示SNHG家族的7个成员（小核仁RNA宿主基因）参与了Notch和PI3K / AKT信号通路。此外，几乎为该家族的所有成员鉴定了几个lncRNA / miRNA / mRNA调控轴。还讨论了其他多功能致癌lncRNA的功能。特别是，已经为TUG1，MALAT1和XIST确定了六到十个这样的轴。使用基因卡，KEGG和Panther数据库，确定了这三种多功能lncRNA靶标的关键信号通路。lncRNA功能的研究有助于开发新的诊断和预后标志物，以治疗骨肉瘤患者。根据现有数据，ceRNA（即miRNA，mRNA和lncRNA）之间的相互作用，