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

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...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-11, Vol.21 (21), p.8322
Main Authors: Karpov, Dmitry S, Spirin, Pavel V, Zheltukhin, Andrey O, Tutyaeva, Vera V, Zinovieva, Olga L, Grineva, Evgenia N, Matrosova, Vera A, Krasnov, George S, Snezhkina, Anastasiya V, Kudryavtseva, Anna V, Prassolov, Vladimir S, Mashkova, Tamara D, Lisitsyn, Nikolai A
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Proliferation - genetics
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Drug Resistance, Neoplasm - genetics
HCT116 Cells
Humans
Neoplasms - genetics
RNA, Long Noncoding - genetics
Signal Transduction - drug effects
Tumor Suppressor Protein p53 - metabolism
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Summary: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 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.
ISSN:1422-0067
1422-0067
DOI:10.3390/ijms21218322