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

eLife

Qinyu Sun¹  Qinyu Hao¹  Kannanganattu V Prasanth¹  Mirit I Aladjem²  Lőrinc Pongor²  Raj Chari³  BinWu Tang⁴  Lisa M Jenkins⁵  Jennifer L Martindale⁶  Myriam Gorospe⁶  Stefan Ambs⁷  Wei Tang⁷  Paul S Meltzer⁸  Robert L Walker⁸  Curtis C Harris⁹  Ana I Robles⁹  Aaron Schetter⁹  Svetlana A Shabalina^1,10  S Perwez Hussain^1,11  Thorkell Andresson^1,12  Sudipto Das^1,12  Corrine CR Hartford^1,13  Ioannis Grammatikakis^1,13  Ashish Lal^1,13  Xiao Ling Li^1,13  Matthew F Jones^1,13  Emily A Dangelmaier^1,13  Bruna R Muys^1,13  Sarah B Lazar^1,13 

[1] Department of Cell and Developmental Biology, Cancer Center at Illinois University of Illinois at Urbana-Champaign, Urbana, United States;Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, United States;Genome Modification Core, Frederick National Lab for Cancer Research, National Cancer Institute, Frederick, United States;Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, United States;Laboratory of Cell Biology, CCR, NCI, NIH, Bethesda, United States;Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, NIH, Baltimore, United States;Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States;Molecular Genetics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, United States;Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States;National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, United States;Pancreatic Cancer Unit, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States;Protein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, United States;Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States;

关键词: lncRNA;    ORF;    FOXA1;    LINC00675;    CRC;    micropeptide;   

DOI  :  10.7554/eLife.53734

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown