LINC00973 Induces Proliferation Arrest of Drug-Treated Cancer Cells by Preventing p21 Degradation.

Autor: Karpov DS; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Spirin PV; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Zheltukhin AO; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Tutyaeva VV; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Zinovieva OL; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia., Grineva EN; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia., Matrosova VA; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia., Krasnov GS; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Snezhkina AV; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Kudryavtseva AV; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Prassolov VS; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia., Mashkova TD; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia., Lisitsyn NA; Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Nov 06; Vol. 21 (21). Date of Electronic Publication: 2020 Nov 06.
DOI: 10.3390/ijms21218322
Abstrakt: Overcoming drug resistance of cancer cells is the major challenge in molecular oncology. Here, we demonstrate that long non-coding RNA LINC00973 is up-regulated in normal and cancer cells of different origins upon treatment with different chemotherapeutics. Bioinformatics analysis shows that this is a consequence of DNA damage response pathway activation or mitotic arrest. Knockdown of LINC0973 decreases p21 levels, activates cellular proliferation of cancer cells, and suppresses apoptosis of drug-treated cells. We have found that LINC00973 strongly increases p21 protein content, possibly by blocking its degradation. Besides, we have found that ectopic over-expression of LINC00973 inhibits formation of the pro-survival p53-Ser15-P isoform, which preserves chromosome integrity. These results might open a new approach to the development of more efficient anti-cancer drugs.
Databáze: MEDLINE
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