A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells
- National Institutes of Health, United States
- University of Illinois at Urbana-Champaign, United States
- NCI, NIH, United States
- National Institute on Aging, NIH, United States
- University of Illinois at Urbana Champaign, United States
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.
Data availability
RNA-seq and ChIP-seq data related to this manuscript has been submitted to GEO under accession number GSE140536.
Article and author information
Author details
Kannanganattu V Prasanth
Funding
National Institutes of Health (ZIA BC 011646)
- Ashish Lal
National Science Foundation (NSF-EAGER)
- Kannanganattu V Prasanth
National Institutes of Health (R01 GM132458)
- Kannanganattu V Prasanth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Maureen E Murphy, The Wistar Institute, United States
Ethics
Animal experimentation: Animal protocols (protocol number LC-070-3) were approved by the National Cancer Institute Animal Care and Use Committee following AALAAC guidelines and policies.
Version history
- Received: November 18, 2019
- Accepted: October 27, 2020
- Accepted Manuscript published: October 28, 2020 (version 1)
- Version of Record published: November 18, 2020 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells
eLife 9:e53734.
https://doi.org/10.7554/eLife.53734
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