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

Autor:	Li XL; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States., Pongor L; Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, United States., Tang W; Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States., Das S; Protein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, United States., Muys BR; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States., Jones MF; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States., Lazar SB; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States., Dangelmaier EA; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States., Hartford CC; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States., Grammatikakis I; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States., Hao Q; Department of Cell and Developmental Biology, Cancer Center at Illinois University of Illinois at Urbana-Champaign, Urbana, United States., Sun Q; Department of Cell and Developmental Biology, Cancer Center at Illinois University of Illinois at Urbana-Champaign, Urbana, United States., Schetter A; Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States., Martindale JL; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, NIH, Baltimore, United States., Tang B; Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, United States., Jenkins LM; Laboratory of Cell Biology, CCR, NCI, NIH, Bethesda, United States., Robles AI; Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States., Walker RL; Molecular Genetics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, United States., Ambs S; Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States., Chari R; Genome Modification Core, Frederick National Lab for Cancer Research, National Cancer Institute, Frederick, United States., Shabalina SA; National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, United States., Gorospe M; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, NIH, Baltimore, United States., Hussain SP; Pancreatic Cancer Unit, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States., Harris CC; Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United States., Meltzer PS; Molecular Genetics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, United States., Prasanth KV; Department of Cell and Developmental Biology, Cancer Center at Illinois University of Illinois at Urbana-Champaign, Urbana, United States., Aladjem MI; Developmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, United States., Andresson T; Protein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, United States., Lal A; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Oct 28; Vol. 9. Date of Electronic Publication: 2020 Oct 28.
DOI:	10.7554/eLife.53734
Abstrakt:	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 ( FO XA1- R egulated C onserved Small P rotein). 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. Competing Interests: XL, LP, WT, BM, MJ, SL, ED, CH, IG, QH, QS, AS, JM, BT, LJ, AR, RW, SA, RC, SS, MG, SH, CH, PM, KP, MA No competing interests declared, SD, TA is affiliated with Leidos Biomedical Research, Inc. AL Reviewing editor, eLife
Databáze:	MEDLINE
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