Long Non-Coding RNAs as Competitive Endogenous RNAs in Osteosarcoma
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Long Non-Coding RNAs as Competitive Endogenous RNAs in Osteosarcoma N. E. Kushlinskiia, M. V. Fridmanb, and E. A. Bragac, d, * a
Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115478 Russia bVavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117971 Russia c Research Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia dResearch Center for Medical Genetics, Moscow, 115478 Russia *e-mail: [email protected] Received April 29, 2020; revised May 17, 2020; accepted May 17, 2020
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. Keywords: miRNAs, long non-coding RNAs, competitive endogenous RNAs, osteosarcoma, signaling pathways DOI: 10.1134/S0026893320050052
Epigenetic mechanisms of gene regulation are involved both in individual development and in various physiological and pathophysiological processes, from aging to tumor genesis and progression. The term “epigenetic” implies that they do not affect the nucleotide sequence of the genome but participate in the regulation of gene expression on different levels [1]. In the last two decades, it has been shown that noncoding RNAs (ncRNAs) play a key role in the regulation of gene expression and cellular signaling pathways under normal and pa
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