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