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

Research paper by Yasuyuki Y Hosono, Yashar S YS Niknafs, John R JR Prensner, Matthew K MK Iyer, Saravana M SM Dhanasekaran, Rohit R Mehra, Sethuramasundaram S Pitchiaya, Jean J Tien, June J Escara-Wilke, Anton A Poliakov, Shih-Chun SC Chu, Sahal S Saleh, Keerthana K Sankar, Fengyun F Su, Shuling S Guo, et al.

Indexed on: 16 Dec '17Published on: 16 Dec '17Published in: Cell



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.