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
Affiliations
Ritu Chaudhary
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Berkley Gryder
Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Wendy S Woods
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, United States
Murugan Subramanian
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Matthew F Jones
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Xiao Ling Li
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Lisa M Jenkins
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Svetlana A Shabalina
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United States
Min Mo
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
Mary Dasso
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
Yuan Yang
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Lalage M Wakefield
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Yuelin Zhu
Molecular Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Susan M Frier
Ionis Pharmaceuticals, Carlsbad, United States
Branden S Moriarity
Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Twin Cities, United States
Kannanganattu V Prasanth
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, United States
Pablo Perez-Pinera
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, United States
Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
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.
