Prosurvival long noncoding RNA <i>PINCR</i> regulates a subset of p53 targets in human colorectal cancer cells by binding to Matrin 3.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28580901.
- Also identified by DOI 10.7554/eLife.23244 and PMC identifier 5470874.
- Licence recorded as CC0.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>PINCR</i> (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) <i>in vitro</i> and tumor growth <i>in vivo</i>. Targeted deletion of <i>PINCR</i> in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. <i>PINCR</i> regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including <i>BTG2, RRM2B</i> and <i>GPX1</i>. Using a novel RNA pulldown approach that utilized endogenous S1-tagged <i>PINCR</i>, we show that <i>PINCR</i> 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/<i>PINCR</i>/Matrin 3 axis in response to DNA damage in CRC cells.
Medical subject headings
- Colorectal Neoplasms
- DNA Damage
- Gene Expression Regulation
- Nuclear Matrix-Associated Proteins
- RNA, Long Noncoding
- RNA-Binding Proteins
- Tumor Suppressor Protein p53