Kushlinskii N E, Fridman M V, Braga E A
Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115478 Russia.
Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117971 Russia.
Mol Biol (Mosk). 2020 Sep-Oct;54(5):776-801. doi: 10.31857/S0026898420050055.
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.
二十多年前，微小RNA（miRNAs）被确认为一类新的RNA，但对其调控作用的理解才刚刚开始显现。此外，人们发现miRNAs作为“主调控因子”的功能可由其他非编码RNA（ncRNAs）控制，特别是长链非编码RNA（lncRNAs）。lncRNAs的调控功能已在各种部位的肿瘤中得到证实，尤其是骨肉瘤，这是青春期儿童最常见、最具侵袭性的恶性骨病。本综述讨论了关于lncRNAs通过竞争性内源性RNA（ceRNAs）机制调控基因表达作用的研究。这些出版物的数据证实了lncRNAs参与了主要信号通路，如Notch、PI3K/AKT、Wnt/β-连环蛋白、JNK和HIV/VEGF。例如，小核仁RNA宿主基因（SNHG）家族的七个成员被证明参与Notch和PI3K/AKT信号通路；此外，几乎该家族的所有成员都鉴定出了几个lncRNA/miRNA/mRNA调控轴。还讨论了其他多功能致癌lncRNAs的功能；特别是，已为TUG1、MALAT1和XIST确定了六到十个这样的轴。利用基因卡片、KEGG和Panther数据库，确定了这三种多功能lncRNAs靶标的关键信号通路。对lncRNA功能的研究有助于开发用于骨肉瘤患者治疗的新诊断和预后标志物。根据现有数据，ceRNAs（即miRNAs、mRNAs和lncRNAs）之间的相互作用代表了一种新的基因表达调控形式，参与了包括骨肿瘤发生在内的各种病理生理过程。
