PUBLICATION
Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA
- Authors
- Hosono, Y., Niknafs, Y.S., Prensner, J.R., Iyer, M.K., Dhanasekaran, S.M., 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, S.M., Bui, H.H., Cao, X., Malik, R., Johnson, T.M., Beer, D.G., Feng, F.Y., Zhou, W., Chinnaiyan, A.M.
- ID
- ZDB-PUB-171216-9
- Date
- 2017
- Source
- Cell 171: 1559-1572.e20 (Journal)
- Registered Authors
- Su, Fengyun, Zhou, Weibin
- Keywords
- IGF2BP1, RNA, RNA-seq, cancer, conservation, fertility, iCLIP, lncRNA, zebrafish
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Disease Models, Animal*
- Gene Knockout Techniques
- Humans
- Male
- Melanoma/metabolism*
- Mice
- RNA, Long Noncoding/metabolism*
- RNA-Binding Proteins/metabolism
- Testis/metabolism
- Zebrafish*
- PubMed
- 29245011 Full text @ Cell
Citation
Hosono, Y., Niknafs, Y.S., Prensner, J.R., Iyer, M.K., Dhanasekaran, S.M., 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, S.M., Bui, H.H., Cao, X., Malik, R., Johnson, T.M., Beer, D.G., Feng, F.Y., Zhou, W., Chinnaiyan, A.M. (2017) Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA. Cell. 171:1559-1572.e20.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping