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

Yasuyuki Hosono, Yashar S. Niknafs, John R. Prensner, Matthew K. Iyer, Saravana M. Dhanasekaran, Rohit Mehra, Sethuramasundaram Pitchiaya, Jean Tien, June Escara-Wilke, Anton Poliakov, Shih Chun Chu, Sahal Saleh, Keerthana Sankar, Fengyun Su, Shuling Guo, Yuanyuan Qiao, Susan M. Freier, Huynh Hoa Bui, Xuhong Cao, Rohit MalikTimothy M. Johnson, David G. Beer, Felix Y. Feng, Weibin Zhou, Arul M. Chinnaiyan

Research output: Contribution to journalArticlepeer-review

148 Citations (Scopus)

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. An ultraconserved lncRNA promotes oncogenesis.

Original languageEnglish
Pages (from-to)1559-1572.e20
JournalCell
Volume171
Issue number7
DOIs
Publication statusPublished - Dec 14 2017
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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