1. Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer
- Author
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Susan M Frier, Wei Tang, Sivasish Sindri, Swetha Parvathaneni, Xinying Zong, Xinyu Wen, Sudha Sharma, Yuelin Zhu, Min Mo, Berkley E. Gryder, Maggie Cam, Jennifer L. Martindale, Ana I. Robles, Lisa M. Miller Jenkins, Dickran Kazandjian, Curtis C. Harris, Aaron J. Schetter, Ritu Chaudhary, Fathi Elloumi, Mary Dasso, Xiaoling Li, Matthew F. Jones, Ashish Lal, Murugan Subramanian, Deepak Singh, Stefan Ambs, Maite Huarte, Frank Rigo, and Kannanganattu V. Prasanth
- Subjects
0301 basic medicine ,p53 ,Cell cycle checkpoint ,LINC01021 ,RP11-46C20.1 ,Colorectal cancer ,Regulator ,LOC643401 ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Basal (phylogenetics) ,lncRNA ,Downregulation and upregulation ,medicine ,Gene silencing ,MYBBP1A ,lcsh:QH301-705.5 ,medicine.disease ,Long non-coding RNA ,CRC ,030104 developmental biology ,lcsh:Biology (General) ,Apoptosis ,lincRNA ,Cancer research ,HuR ,PURPL - Abstract
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 auto-regulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels.
- Published
- 2017