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Open AccessArticle

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

1
Engelhard Institute of Molecular Biology, Russian Academy of Sciences, 111991 Moscow, Russia
2
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhard Institute of Molecular Biology, 111991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(21), 8322; https://doi.org/10.3390/ijms21218322
Received: 9 October 2020 / Revised: 31 October 2020 / Accepted: 4 November 2020 / Published: 6 November 2020
(This article belongs to the Collection Feature Papers in Molecular Oncology)
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. View Full-Text
Keywords: LINC00973; DDR; CRC; 5-FU; p21 LINC00973; DDR; CRC; 5-FU; p21
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Karpov, D.S.; Spirin, P.V.; Zheltukhin, A.O.; Tutyaeva, V.V.; Zinovieva, O.L.; Grineva, E.N.; Matrosova, V.A.; Krasnov, G.S.; Snezhkina, A.V.; Kudryavtseva, A.V.; Prassolov, V.S.; Mashkova, T.D.; Lisitsyn, N.A. LINC00973 Induces Proliferation Arrest of Drug-Treated Cancer Cells by Preventing p21 Degradation. Int. J. Mol. Sci. 2020, 21, 8322.

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