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

Int J Mol Sci. 2020 Nov 6;21(21):8322. doi: 10.3390/ijms21218322.

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.

Keywords: 5-FU; CRC; DDR; LINC00973; p21.

MeSH terms

  • 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

Substances

  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Long Noncoding
  • Tumor Suppressor Protein p53