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

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

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.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal*
  • Gene Knockout Techniques
  • Humans
  • Male
  • Melanoma / metabolism*
  • Mice
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / metabolism
  • Testis / metabolism
  • Zebrafish*

Substances

  • IMP-1 protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins