Adversary of DNA integrity: A long non-coding RNA stimulates driver oncogenic chromosomal rearrangement in human thyroid cells.

Autor:	Demin DE; Laboratory for the Transmission of Intracellular Signals in Normal and Pathological Conditions, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Murashko MM; Laboratory for the Transmission of Intracellular Signals in Normal and Pathological Conditions, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Moscow, Russia., Uvarova AN; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia., Stasevich EM; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Shyrokova EY; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Moscow, Russia.; Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Gorlachev GE; GBUZ Moscow Clinical Scientific Center named after Loginov MHD., Zaretsky AR; Department of Molecular Technologies, Research Institute of Translational Medicine, N. I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation., Korneev KV; Laboratory for the Transmission of Intracellular Signals in Normal and Pathological Conditions, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.; National Research Center for Hematology, Moscow, Russia., Ustiugova AS; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Tkachenko EA; Laboratory for the Transmission of Intracellular Signals in Normal and Pathological Conditions, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia., Kostenko VV; Laboratory for the Transmission of Intracellular Signals in Normal and Pathological Conditions, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia., Tatosyan KA; Laboratory of Eukaryotic Genome Evolution, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Sheetikov SA; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.; National Research Center for Hematology, Moscow, Russia., Spirin PV; Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kuprash DV; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia., Schwartz AM; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	International journal of cancer [Int J Cancer] 2023 Apr 01; Vol. 152 (7), pp. 1452-1462. Date of Electronic Publication: 2023 Jan 16.
DOI:	10.1002/ijc.34396
Abstrakt:	The flurry of publications devoted to the functions of long non-coding RNAs (lncRNAs) published in the last decade leaves no doubt about the exceptional importance of lncRNAs in various areas including tumor biology. However, contribution of lncRNAs to the early stages of oncogenesis remains poorly understood. In this study we explored a new role for lncRNAs: stimulation of specific chromosomal rearrangements upon DNA damage. We demonstrated that lncRNA CASTL1 (ENSG00000269945) stimulates the formation of the CCDC6-RET inversion (RET/PTC1) in human thyroid cells subjected to radiation or chemical DNA damage. Facilitation of chromosomal rearrangement requires lncRNA to contain regions complementary to the introns of both CCDC6 and RET genes as deletion of these regions deprives CASTL1 of the ability to stimulate the gene fusion. We found that CASTL1 expression is elevated in tumors with CCDC6-RET fusion which is the most frequent rearrangement in papillary thyroid carcinoma. Our results open a new venue for the studies of early oncogenesis in various tumor types, especially those associated with physical or chemical DNA damage. (© 2022 UICC.)
Databáze:	MEDLINE
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