Cell Reports (Sep 2017)
Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer
- Xiao Ling Li,
- Murugan Subramanian,
- Matthew F. Jones,
- Ritu Chaudhary,
- Deepak K. Singh,
- Xinying Zong,
- Berkley Gryder,
- Sivasish Sindri,
- Min Mo,
- Aaron Schetter,
- Xinyu Wen,
- Swetha Parvathaneni,
- Dickran Kazandjian,
- Lisa M. Jenkins,
- Wei Tang,
- Fathi Elloumi,
- Jennifer L. Martindale,
- Maite Huarte,
- Yuelin Zhu,
- Ana I. Robles,
- Susan M. Frier,
- Frank Rigo,
- Maggie Cam,
- Stefan Ambs,
- Sudha Sharma,
- Curtis C. Harris,
- Mary Dasso,
- Kannanganattu V. Prasanth,
- Ashish Lal
Affiliations
- Xiao Ling Li
- Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA
- Murugan Subramanian
- Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA
- Matthew F. Jones
- Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA
- Ritu Chaudhary
- Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA
- Deepak K. Singh
- Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Xinying Zong
- Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Berkley Gryder
- Oncogenomics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Sivasish Sindri
- Oncogenomics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Min Mo
- Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
- Aaron Schetter
- Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Xinyu Wen
- Oncogenomics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Swetha Parvathaneni
- Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, Washington, DC 20059, USA
- Dickran Kazandjian
- Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Lisa M. Jenkins
- Laboratory of Cell Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Wei Tang
- Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Fathi Elloumi
- Office of Science and Technology Resources, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Jennifer L. Martindale
- Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
- Maite Huarte
- Center for Applied Medical Research, Department of Gene Therapy and Regulation of Gene Expression, University of Navarra, 31008 Pamplona, Spain
- Yuelin Zhu
- Molecular Genetics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, MD 28092, USA
- Ana I. Robles
- Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Susan M. Frier
- Ionis Pharmaceuticals, Carlsbad, CA 92010, USA
- Frank Rigo
- Ionis Pharmaceuticals, Carlsbad, CA 92010, USA
- Maggie Cam
- Office of Science and Technology Resources, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Stefan Ambs
- Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Sudha Sharma
- Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, Washington, DC 20059, USA
- Curtis C. Harris
- Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892, USA
- Mary Dasso
- Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
- Kannanganattu V. Prasanth
- Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Ashish Lal
- Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA
- DOI
- https://doi.org/10.1016/j.celrep.2017.08.041
- Journal volume & issue
-
Vol. 20,
no. 10
pp. 2408 – 2423
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.
Keywords
