期刊
CELL
卷 171, 期 7, 页码 1559-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2017.11.040
关键词
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资金
- National Cancer Institute Early Detection Research Network [U01CA214170]
- U.S. National Institutes of Health (NIH) [RO1 CA154365]
- Genentech Fellowship
- Prostate Cancer Foundation
- U.S. Department of Defense [W81XWH-13-1-0284]
- University of Michigan Cellular and Molecular Biology National Research Service Award Institutional Predoctoral Training Grant
- NIH [DK091405, DK081943, F30-CA-200328]
- Janette Ferrantino Investigator Award
- American Society of Nephrology Carl W. Gottschalk Scholar Research Grant
Large-scale transcriptome sequencing efforts have vastly expanded the catalog of long non-coding RNAs (lncRNAs) with varying evolutionary conservation, lineage expression, and cancer specificity. Here, we functionally characterize a novel ultra-conserved lncRNA, THOR (ENSG00000226856), which exhibits expression exclusively in testis and a broad range of human cancers. THOR knockdown and overexpression in multiple cell lines and animal models alters cell or tumor growth supporting an oncogenic role. We discovered a conserved interaction of THOR with IGF2BP1 and show that THOR contributes to the mRNA stabilization activities of IGF2BP1. Notably, transgenic THOR knockout produced fertilization defects in zebrafish and also conferred a resistance to melanoma onset. Likewise, ectopic expression of human THOR in zebrafish accelerated the onset of melanoma. THOR represents a novel class of functionally important cancer/testis lncRNAs whose structure and function have undergone positive evolutionary selection.
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