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REVIEW: Molecular Mechanisms and microRNAs in Osteosarcoma Pathogenesis

N. E. Kushlinskii1, M. V. Fridman2, and E. A. Braga3*

1Blokhin Cancer Research Center, 115478 Moscow, Russia; fax: +7 (499) 324-6352; E-mail: biochimia@mtu-net.ru

2Vavilov Institute of General Genetics, Russian Academy of Sciences, 117971 Moscow, Russia; fax: +7 (499) 135-6213; E-mail: iogen@vigg.ru

3Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia; fax: +7 (495) 601-2366; E-mail: eleonora10_45@mail.ru

* To whom correspondence should be addressed.

Received October 19, 2015; Revision received November 3, 2015
This review summarizes data on microRNA (miRNA) genomic organization, biogenesis, and functions in carcinogenesis. The roles of key genes and regulatory miRNAs in molecular mechanisms and signaling pathways involved in the development of osteosarcoma, the most aggressive type of bone tumor striking mainly in adolescence and early adulthood, are discussed in detail. The most critical pathways in osteosarcoma pathogenesis are the Notch, Wnt, NF-κB, p53, PI3K/Akt, and MAPK pathways. The balance between cell survival and apoptosis is determined by the Wnt and NF-κB pathways, as well as by the ratio between the activities of the MAPK and PI3K/Akt pathways. Several miRNAs (miR-21, -34a, -143, -148a, -195a, -199a-3p, -382) regulate multiple target genes, pathways, and processes essential for osteosarcoma pathogenesis. Data on the key genes and regulatory miRNAs involved in metastasis and tumor cell response to drug treatment are presented. Possible applications of miRNA in osteosarcoma diagnostics and treatment are discussed.
KEY WORDS: regulatory miRNAs, key genes, oncogenesis, signaling pathways, osteosarcoma, metastasis

DOI: 10.1134/S0006297916040027