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A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells

  1. Author:
    Li, Xiao Ling
    Pongor, Lorinc
    Tang, Wei
    Das,Sudipto
    Muys, Bruna R
    Jones, Matthew F
    Lazar, Sarah B
    Dangelmaier, Emily A
    Hartford, Corrine Cr
    Grammatikakis, Ioannis
    Hao, Qinyu [ORCID]
    Sun, Qinyu
    Schetter, Aaron
    Martindale, Jennifer L
    Tang, BinWu
    Jenkins, Lisa M
    Robles, Ana I
    Walker, Robert L
    Ambs, Stefan
    Chari,Raj
    Shabalina, Svetlana A
    Gorospe, Myriam
    Hussain, Perwez S
    Harris, Curtis C
    Meltzer, Paul S
    Prasanth, Kannanganattu V [ORCID]
    Aladjem, Mirit I
    Andresson,Thorkell
    Lal, Ashish [ORCID]
  2. Author Address

    Regulatory RNAs and Cancer Section Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Developmental Therapeutics Branch, CCR, NCI, National Institutes of Health, Bethesda, United States., Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, United States., Protein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.,, National Institutes of Health, Frederick, United States., Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Department of Cell and Developmental Biology, Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, United States., Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, United States., Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, United States., Laboratory of Cancer Biology and Genetics, CCR, NCI, National Institutes of Health, Bethesda, United States., Laboratory of Cell Biology, CCR, NCI, National Institutes of Health, Bethesda, United States., Molecular Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Genome Modification Core, Frederick National Lab for Cancer Research, NCI, NIH, Bethesda, United States., National Center for Biotechnology Information, National Institutes of Health, Bethesda, United States., Intramural Research Program, National Institute on Aging, NIH, Baltimore, United States., Pancreatic Cancer Unit at the Laboratory of Human Carcinogenesis, CCR, NCI, National Institutes of Health, Bethesda, United States., Cell and Developmental Biology, University of Illinois at Urbana Champaign, Urbana, United States.,
    1. Year: 2020
    2. Date: Oct 28
    3. Epub Date: 2020 10 28
  1. Journal: eLife
    1. 9
    2. Pages: pii: e53734.
  2. Type of Article: Article
  3. Article Number: ARTN e53734
  4. ISSN: 2050-084X
  1. Abstract:

    Long noncoding RNAs (lncRNAs) are often associated with polysomes, indicating coding potential. However, only a handful of endogenous proteins encoded by putative lncRNAs have been identified and assigned a function. Here, we report the discovery of a putative gastrointestinal tract-specific lncRNA (LINC00675) that is regulated by the pioneer transcription factor FOXA1 and encodes a conserved small protein of 79 amino acids which we termed FORCP (FOXA1-Regulated Conserved Small Protein). FORCP transcript is undetectable in most cell types but is abundant in well-differentiated colorectal cancer (CRC) cells where it functions to inhibit proliferation, clonogenicity and tumorigenesis. The epitope-tagged and endogenous FORCP protein predominantly localizes to the endoplasmic reticulum (ER). In response to ER stress, FORCP depletion results in decreased apoptosis. Our findings on the initial characterization of FORCP demonstrate that FORCP is a novel, conserved small protein encoded by a mis-annotated lncRNA that regulates apoptosis and tumorigenicity in well-differentiated CRC cells.

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External Sources

  1. DOI: 10.7554/eLife.53734
  2. PMID: 33112233
  3. WOS: 000592842800001
  4. PII : 53734

Library Notes

  1. Fiscal Year: FY2020-2021
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