Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3

Ritu Chaudhary, Berkley Gryder, Wendy S. Woods, Murugan Subramanian, Matthew F. Jones, Xiao Ling Li, Lisa M. Jenkins, Svetlana A. Shabalina, Min Mo, Mary Dasso, Yuan Yang, Lalage M. Wakefield, Yuelin Zhu, Susan M. Frier, Branden S. Moriarity, Kannanganattu V. Prasanth, Pablo Perez-Pinera, Ashish Lal

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells.

Original languageEnglish (US)
Article numbere23244
JournaleLife
Volume6
DOIs
StatePublished - Jun 5 2017

Bibliographical note

Funding Information:
We thank Tom Misteli, Glenn Merlino, Susan Gottesman, Shiv Grewal, Curtis Harris and Javed Khan for their critical comments on the manuscript and Bert Vogelstein for the isogenic cell lines. This research was supported by the Intramural Research Program (AL, LW, LMJ) of the National Cancer Institute (NCI), Center for Cancer Research (CCR), NIH. KVP lab is supported by grants from NIH [GM088252] and American Cancer Society [RSG-11-174-01-RMC]. National Cancer InstituteNIH IRP Ashish Lal.

Publisher Copyright:
© 2017, eLife Sciences Publications Ltd. All rights reserved.

Fingerprint

Dive into the research topics of 'Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3'. Together they form a unique fingerprint.

Cite this