Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA.
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.
Hosono, Y; Niknafs, YS; Prensner, JR; Iyer, MK; Dhanasekaran, SM; 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, SM; Bui, H-H; Cao, X; Malik, R; Johnson, TM; Beer, DG; Feng, FY; Zhou, W; Chinnaiyan, AM
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