Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

Abstract

SUMMARY Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated p53 levels to induce cell cycle arrest, apoptosis and tumor suppression. Here, we report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that we termed PURPL (p53 upregulated regulator of p53 levels). Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induces growth defects in cell culture and in mouse xenografts. PURPL associates with MYBBP1A, a protein that binds to and stabilizes p53, and inhibits the formation of the p53-MYBBP1A complex. In the absence of PURPL, MYBBP1A interacts with and stabilizes p53. Silencing MYBBP1A significantly rescues basal p53 levels and proliferation in PURPL-deficient cells, suggesting that MYBBP1A mediates the effect of PURPL in regulating p53. These results reveal a p53-PURPL autoregulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels.

Lnc-SNHG1 Activates the TGFBR2/SMAD3 and RAB11A/Wnt/β-Catenin Pathway by Sponging MiR-302/372/373/520 in Invasive Pituitary Tumors

“…In short, subcutaneous tumor xenografting was performed by injecting the right flank of nude mice with 1×10 7 cells that had been transfected with the indicated plasmids. After 4 weeks, the mice were sacrificed, and …”

An LTR retrotransposon‐derived lnc RNA interacts with RNF 169 to promote homologous recombination

“…As expected, we found that the expression of PRLH1 increased nearly up to eightfold in SK-HEP-1 cells, while remaining unchanged in HuH-7 cells after knockdown of p53 by siRNA ( Fig 1F). Notably, the knockout of p53 in HepG2 cells led to a remarkable decrease in the expression of the known p53-activated lncRNA PURPL [40] and a significant increase in the expression of other three lncRNAs (AC073236.3, RP11-81H3.2, and RP11-328N19.1) displayed in Fig 1C (Appendix Fig S1G), indicating that these three lncRNAs were also repressed directly or indirectly by wild-type p53. Notably, the knockout of p53 in HepG2 cells led to a remarkable decrease in the expression of the known p53-activated lncRNA PURPL [40] and a significant increase in the expression of other three lncRNAs (AC073236.3, RP11-81H3.2, and RP11-328N19.1) displayed in Fig 1C (Appendix Fig S1G), indicating that these three lncRNAs were also repressed directly or indirectly by wild-type p53.…”

Multi-leveled suppression of p53 function by HuR lncRNPs

“…In a recent issue of Cell Reports, Li et al (22) identified and functionally characterized the p53-regulated lncRNA PURPL in colorectal cancer. PURPL was strongly induced by DNA damage and was predominant in nuclear.…”

“…By RNA pulldown and mass spectrometry, Li et al (22) found strong interaction between PURPL and MYBBP1A, a protein that stabilizes p53. In light of the authors’ result that loss of PURPL increased p53 levels, they proposed that loss of PURPL freed up MYBBP1A, enabling it to bind and increase p53 stability.…”

“…However, the studies by Yoon (10) and Li (22) discussed here bring into focus HuR as an RBP that can jointly suppress p53 function and reduce p53 levels. With escalating interest in developing therapies that raise p53 activity, particularly in combination with DNA-damaging treatments, new lines of effort could be devised based on these findings.…”