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

Dmitry S KarpovPavel V SpirinAndrey O ZheltukhinVera V TutyaevaOlga L ZinovievaEvgenia N GrinevaVera A MatrosovaGeorge S KrasnovAnastasiya V SnezhkinaAnna V KudryavtsevaVladimir S PrassolovTamara D MashkovaNikolai A Lisitsyn
Published in: International journal of molecular sciences (2020)
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.
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