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 & 9 others Susan M. Frier, Frank Rigo, Maggie Cam, Stefan Ambs, Sudha Sharma, Curtis C. Harris, Mary Dasso, Kannanganattu V. Prasanth, Ashish Lal

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2408-2423
Number of pages16
JournalCell Reports
Volume20
Issue number10
DOIs
Publication statusPublished - 5 Sep 2017
Externally publishedYes

Fingerprint

Long Noncoding RNA
Colorectal Neoplasms
Cells
Cell Cycle Checkpoints
Cell culture
Heterografts
Tumors
Cell Culture Techniques
Apoptosis
Feedback
Defects
Growth
Neoplasms
Proteins

Keywords

  • CRC
  • HuR
  • LINC01021
  • lincRNA
  • lncRNA
  • LOC643401
  • MYBBP1A
  • p53
  • PURPL
  • RP11-46C20.1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer. / Li, Xiao Ling; Subramanian, Murugan; Jones, Matthew F.; Chaudhary, Ritu; Singh, Deepak K.; Zong, Xinying; Gryder, Berkley; Sindri, Sivasish; Mo, Min; Schetter, Aaron; Wen, Xinyu; Parvathaneni, Swetha; Kazandjian, Dickran; Jenkins, Lisa M.; Tang, Wei; Elloumi, Fathi; Martindale, Jennifer L.; Huarte, Maite; Zhu, Yuelin; Robles, Ana I.; Frier, Susan M.; Rigo, Frank; Cam, Maggie; Ambs, Stefan; Sharma, Sudha; Harris, Curtis C.; Dasso, Mary; Prasanth, Kannanganattu V.; Lal, Ashish.

In: Cell Reports, Vol. 20, No. 10, 05.09.2017, p. 2408-2423.

Research output: Contribution to journalArticle

Li, XL, Subramanian, M, Jones, MF, Chaudhary, R, Singh, DK, Zong, X, Gryder, B, Sindri, S, Mo, M, Schetter, A, Wen, X, Parvathaneni, S, Kazandjian, D, Jenkins, LM, Tang, W, Elloumi, F, Martindale, JL, Huarte, M, Zhu, Y, Robles, AI, Frier, SM, Rigo, F, Cam, M, Ambs, S, Sharma, S, Harris, CC, Dasso, M, Prasanth, KV & Lal, A 2017, 'Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer', Cell Reports, vol. 20, no. 10, pp. 2408-2423. https://doi.org/10.1016/j.celrep.2017.08.041
Li, Xiao Ling ; Subramanian, Murugan ; Jones, Matthew F. ; Chaudhary, Ritu ; Singh, Deepak K. ; Zong, Xinying ; Gryder, Berkley ; Sindri, Sivasish ; Mo, Min ; Schetter, Aaron ; Wen, Xinyu ; Parvathaneni, Swetha ; Kazandjian, Dickran ; Jenkins, Lisa M. ; Tang, Wei ; Elloumi, Fathi ; Martindale, Jennifer L. ; Huarte, Maite ; Zhu, Yuelin ; Robles, Ana I. ; Frier, Susan M. ; Rigo, Frank ; Cam, Maggie ; Ambs, Stefan ; Sharma, Sudha ; Harris, Curtis C. ; Dasso, Mary ; Prasanth, Kannanganattu V. ; Lal, Ashish. / Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer. In: Cell Reports. 2017 ; Vol. 20, No. 10. pp. 2408-2423.
@article{43675c88dbd74a588b109d4e9e824b9e,
title = "Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer",
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 = "CRC, HuR, LINC01021, lincRNA, lncRNA, LOC643401, MYBBP1A, p53, PURPL, RP11-46C20.1",
author = "Li, {Xiao Ling} and Murugan Subramanian and Jones, {Matthew F.} and Ritu Chaudhary and Singh, {Deepak K.} and Xinying Zong and Berkley Gryder and Sivasish Sindri and Min Mo and Aaron Schetter and Xinyu Wen and Swetha Parvathaneni and Dickran Kazandjian and Jenkins, {Lisa M.} and Wei Tang and Fathi Elloumi and Martindale, {Jennifer L.} and Maite Huarte and Yuelin Zhu and Robles, {Ana I.} and Frier, {Susan M.} and Frank Rigo and Maggie Cam and Stefan Ambs and Sudha Sharma and Harris, {Curtis C.} and Mary Dasso and Prasanth, {Kannanganattu V.} and Ashish Lal",
year = "2017",
month = "9",
day = "5",
doi = "10.1016/j.celrep.2017.08.041",
language = "English",
volume = "20",
pages = "2408--2423",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",

}

TY - JOUR

T1 - Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

AU - Li, Xiao Ling

AU - Subramanian, Murugan

AU - Jones, Matthew F.

AU - Chaudhary, Ritu

AU - Singh, Deepak K.

AU - Zong, Xinying

AU - Gryder, Berkley

AU - Sindri, Sivasish

AU - Mo, Min

AU - Schetter, Aaron

AU - Wen, Xinyu

AU - Parvathaneni, Swetha

AU - Kazandjian, Dickran

AU - Jenkins, Lisa M.

AU - Tang, Wei

AU - Elloumi, Fathi

AU - Martindale, Jennifer L.

AU - Huarte, Maite

AU - Zhu, Yuelin

AU - Robles, Ana I.

AU - Frier, Susan M.

AU - Rigo, Frank

AU - Cam, Maggie

AU - Ambs, Stefan

AU - Sharma, Sudha

AU - Harris, Curtis C.

AU - Dasso, Mary

AU - Prasanth, Kannanganattu V.

AU - Lal, Ashish

PY - 2017/9/5

Y1 - 2017/9/5

N2 - 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.

AB - 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.

KW - CRC

KW - HuR

KW - LINC01021

KW - lincRNA

KW - lncRNA

KW - LOC643401

KW - MYBBP1A

KW - p53

KW - PURPL

KW - RP11-46C20.1

UR - http://www.scopus.com/inward/record.url?scp=85028880966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028880966&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.08.041

DO - 10.1016/j.celrep.2017.08.041

M3 - Article

VL - 20

SP - 2408

EP - 2423

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 10

ER -