Oncogenic Role of THOR, a Conserved Cancer/Testis Long Noncoding RNA

• Published in: Cell 2017-12, Vol.171 (7), p.1559-1572.e20
• Main Authors: Hosono, Yasuyuki, Niknafs, Yashar S, Prensner, John R, Iyer, Matthew K, Dhanasekaran, Saravana M, Mehra, Rohit, Pitchiaya, Sethuramasundaram, Tien, Jean, Escara-Wilke, June, Poliakov, Anton, Chu, Shih-Chun, Saleh, Sahal, Sankar, Keerthana, Su, Fengyun, Guo, Shuling, Qiao, Yuanyuan, Freier, Susan M, Bui, Huynh-Hoa, Cao, Xuhong, Malik, Rohit, Johnson, Timothy M, Beer, David G, Feng, Felix Y, Zhou, Weibin, Chinnaiyan, Arul M
• Format: Article
• Language: English
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2017.11.040

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.