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Cell. 2017 Dec 14;171(7):1559-1572.e20. doi: 10.1016/j.cell.2017.11.040.

Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA.

Author information

1
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
2
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA.
3
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
4
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
5
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
6
Department of Urology, University of Michigan, Ann Arbor, MI, USA.
7
Ionis Pharmaceuticals, Carlsbad, CA, USA.
8
Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
9
Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
10
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
11
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
12
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan, Ann Arbor, MI, USA. Electronic address: arul@med.umich.edu.

Abstract

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 ultraconserved 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.

KEYWORDS:

IGF2BP1; RNA; RNA-seq; cancer; conservation; fertility; iCLIP; lncRNA; zebrafish

PMID:
29245011
PMCID:
PMC5734106
[Available on 2018-12-14]
DOI:
10.1016/j.cell.2017.11.040
[Indexed for MEDLINE]

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