ZFIN ID: ZDB-PUB-171216-9
Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA
Hosono, Y., Niknafs, Y.S., Prensner, J.R., Iyer, M.K., Dhanasekaran, S.M., Mehra, R., Pitchiaya, S., Tien, J., Escara-Wilke, J., Poliakov, A., Chu, S.C., Saleh, S., Sankar, K., Su, F., Guo, S., Qiao, Y., Freier, S.M., Bui, H.H., Cao, X., Malik, R., Johnson, T.M., Beer, D.G., Feng, F.Y., Zhou, W., Chinnaiyan, A.M.
Date: 2017
Source: Cell   171: 1559-1572.e20 (Journal)
Registered Authors: Su, Fengyun, Zhou, Weibin
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*
PubMed: 29245011 Full text @ Cell
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.