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

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 (<i>LINC00675</i>) that is regulated by the pioneer transcription factor FOXA1 and encodes a conserved small protein of 79 amino acids which we termed FORCP (<i>FO</i>XA1-<i>R</i>egulated <i>C</i>onserved Small <i>P</i>rotein). <i>FORCP</i> 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, <i>FORCP</i> depletion results in decreased apoptosis. Our findings on the initial characterization of <i>FORCP</i> 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.