1. LINC00973 Induces Proliferation Arrest of Drug-Treated Cancer Cells by Preventing p21 Degradation.
- Author
-
Karpov DS, Spirin PV, Zheltukhin AO, Tutyaeva VV, Zinovieva OL, Grineva EN, Matrosova VA, Krasnov GS, Snezhkina AV, Kudryavtseva AV, Prassolov VS, Mashkova TD, and Lisitsyn NA
- Subjects
- Antineoplastic Agents pharmacology, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation genetics, Cyclin-Dependent Kinase Inhibitor p21 metabolism, HCT116 Cells, Humans, Signal Transduction drug effects, Tumor Suppressor Protein p53 metabolism, Drug Resistance, Neoplasm genetics, Neoplasms genetics, RNA, Long Noncoding genetics
- Abstract
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.
- Published
- 2020
- Full Text
- View/download PDF