Long Non-coding RNA, PANDA, Contributes to the Stabilization of p53 Tumor Suppressor Protein

Anticancer Res. 2016 Apr;36(4):1605-11.

Abstract

Background: P21-associated noncoding RNA DNA damage-activated (PANDA) is induced in response to DNA damage and represses apoptosis by inhibiting the function of nuclear transcription factor Y subunit alpha (NF-YA) transcription factor. Herein, we report that PANDA affects regulation of p53 tumor-suppressor protein.

Materials and methods: U2OS cells were transfected with PANDA siRNAs. At 72 h post-transfection, cells were subjected to immunoblotting and quantitative reverse transcription-polymerase chain reaction.

Results: Depletion of PANDA was associated with decreased levels of p53 protein, but not p53 mRNA. The stability of p53 protein was markedly reduced by PANDA silencing. Degradation of p53 protein by silencing PANDA was prevented by treatment of MG132, a proteasome inhibitor. Moreover, depletion of PANDA prevented accumulation of p53 protein, as a result of DNA damage, induced by the genotoxic agent etoposide.

Conclusion: These results suggest that PANDA stabilizes p53 protein in response to DNA damage, and provide new insight into the regulatory mechanisms of p53.

Keywords: Long non-coding RNA; PANDA; p53; protein degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Damage
  • Etoposide / pharmacology
  • Humans
  • Mutagens / pharmacology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Mutagens
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Etoposide