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Long Non-Coding RNAs as Competitive Endogenous RNAs in Osteosarcoma

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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.

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Funding

This work was supported by the Ministry of Science and Education of the Russian Federation via State Assignment to the Institute and the Ministry of Health of the Russian Federation for 2020.

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Authors and Affiliations

  1. Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, 115478, Moscow, Russia

    N. E. Kushlinskii

  2. Vavilov Institute of General Genetics, Russian Academy of Sciences, 117971, Moscow, Russia

    M. V. Fridman

  3. Research Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia

    E. A. Braga

  4. Research Center for Medical Genetics, 115478, Moscow, Russia

    E. A. Braga

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  1. N. E. Kushlinskii
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  3. E. A. Braga
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Correspondence to E. A. Braga.

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Translated by D. Timchenko

Abbreviations: OS, osteosarcoma; ceRNA, competitive endogenous RNA; lncRNA, long non-coding RNA; EMT, epithelial–mesenchymal transition; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; SNHG, small nucleolar RNA host gene; TUG1, Taurine upregulated 1; XIST, X inactive-specific transcript; 3'-UTR, 3'-untranslated region.

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Kushlinskii, N.E., Fridman, M.V. & Braga, E.A. Long Non-Coding RNAs as Competitive Endogenous RNAs in Osteosarcoma. Mol Biol 54, 684–707 (2020). https://doi.org/10.1134/S0026893320050052

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