A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells
| Autor: | Stefan Ambs, Robert L. Walker, Sudipto Das, Xiaoling Li, Corrine Corrina R. Hartford, Lisa M. Miller Jenkins, Lorinc Pongor, Sarah B. Lazar, Raj Chari, Perwez Hussain, Qinyu Hao, Ana I. Robles, Thorkell Andresson, Qinyu Sun, Bruna Rodrigues Muys, Paul S. Meltzer, Matthew F. Jones, Ashish Lal, Emily A. Dangelmaier, Svetlana A. Shabalina, Jennifer L. Martindale, Binwu Tang, Ioannis Grammatikakis, Mirit I. Aladjem, Wei Tang, Myriam Gorospe, Kannanganattu V. Prasanth, Aaron J. Schetter, Curtis C. Harris |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Carcinogenesis Apoptosis LINC00675 Endoplasmic Reticulum medicine.disease_cause lncRNA 0302 clinical medicine Genes Reporter Gene expression Biology (General) Cancer Biology General Neuroscience General Medicine Endoplasmic Reticulum Stress Chromosomes and Gene Expression CRC micropeptide Cell biology Organ Specificity 030220 oncology & carcinogenesis Medicine RNA Long Noncoding Colorectal Neoplasms ORF Research Article Human Hepatocyte Nuclear Factor 3-alpha Cell type QH301-705.5 Science Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cell Line Tumor Polysome medicine Humans Transcription factor Cell Proliferation General Immunology and Microbiology Endoplasmic reticulum Molecular Sequence Annotation Gastrointestinal Tract 030104 developmental biology Unfolded protein response FOXA1 |
| Zdroj: | eLife eLife, Vol 9 (2020) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.53734 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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