Early Detection Research Network

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.

Beer DG, Bui HH, Cao X, Chinnaiyan AM, Chu SC, Dhanasekaran SM, Escara-Wilke J, Feng FY, Freier SM, Guo S, Hosono Y, Iyer MK, Johnson TM, Malik R, Mehra R, Niknafs YS, Pitchiaya S, Poliakov A, Prensner JR, Qiao Y, Saleh S, Sankar K, Su F, Tien J, Zhou W

29245011

Cell, 2017, 171 (7)