@article{33ac86ba9b7e4c63be336776102739db,
title = "Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA",
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. An ultraconserved lncRNA promotes oncogenesis.",
keywords = "IGF2BP1, RNA, RNA-seq, cancer, conservation, fertility, iCLIP, lncRNA, zebrafish",
author = "Yasuyuki Hosono and Niknafs, {Yashar S.} and Prensner, {John R.} and Iyer, {Matthew K.} and Dhanasekaran, {Saravana M.} and Rohit Mehra and Sethuramasundaram Pitchiaya and Jean Tien and June Escara-Wilke and Anton Poliakov and Chu, {Shih Chun} and Sahal Saleh and Keerthana Sankar and Fengyun Su and Shuling Guo and Yuanyuan Qiao and Freier, {Susan M.} and Bui, {Huynh Hoa} and Xuhong Cao and Rohit Malik and Johnson, {Timothy M.} and Beer, {David G.} and Feng, {Felix Y.} and Weibin Zhou and Chinnaiyan, {Arul M.}",
note = "Funding Information: We thank S. Shukla, L. Xiao, A. Delekta, and Y. Zhang for technical assistance; J. Shavit and S. Kregel for discussion; and T. Saunders for mice embryos. This work was supported in part by the National Cancer Institute Early Detection Research Network ( U01CA214170 ) and U.S. National Institutes of Health (NIH) grant RO1 CA154365 (D.G.B. and A.M.C.). A.M.C. is an American Cancer Society Research Professor, a Howard Hughes Medical Institute Investigator, and a Taubman Scholar of the University of Michigan. Y.H. was supported by a Genentech Fellowship. R. Malik is supported by a Prostate Cancer Foundation Young Investigator Award and by U.S. Department of Defense Postdoctoral Fellowship W81XWH-13-1-0284 . Y.S.N. was supported by a University of Michigan Cellular and Molecular Biology National Research Service Award Institutional Predoctoral Training Grant and by a Prostate Cancer Foundation Young Investigator Award. W.Z. was supported by grants from the NIH ( DK091405 , DK081943 sub ), the Janette Ferrantino Investigator Award, and the American Society of Nephrology Carl W. Gottschalk Scholar Research Grant. Y.S.N. is supported by an NIH F30 grant ( F30-CA-200328 ). S.G., S.M.F., and H.-H.B. are employees of Ionis Pharmaceuticals, which may develop therapeutic ASO compounds against THOR. The University of Michigan will file a patent on THOR as a target and has filed a related technology disclosure around lncRNAs diagnostics in cancer. A.M.C., Y.H., and Y.S.N. will be named co-inventors. Funding Information: We thank S. Shukla, L. Xiao, A. Delekta, and Y. Zhang for technical assistance; J. Shavit and S. Kregel for discussion; and T. Saunders for mice embryos. This work was supported in part by the National Cancer Institute Early Detection Research Network (U01CA214170) and U.S. National Institutes of Health (NIH) grant RO1 CA154365 (D.G.B. and A.M.C.). A.M.C. is an American Cancer Society Research Professor, a Howard Hughes Medical Institute Investigator, and a Taubman Scholar of the University of Michigan. Y.H. was supported by a Genentech Fellowship. R. Malik is supported by a Prostate Cancer Foundation Young Investigator Award and by U.S. Department of Defense Postdoctoral Fellowship W81XWH-13-1-0284. Y.S.N. was supported by a University of Michigan Cellular and Molecular Biology National Research Service Award Institutional Predoctoral Training Grant and by a Prostate Cancer Foundation Young Investigator Award. W.Z. was supported by grants from the NIH (DK091405, DK081943 sub), the Janette Ferrantino Investigator Award, and the American Society of Nephrology Carl W. Gottschalk Scholar Research Grant. Y.S.N. is supported by an NIH F30 grant (F30-CA-200328). S.G., S.M.F., and H.-H.B. are employees of Ionis Pharmaceuticals, which may develop therapeutic ASO compounds against THOR. The University of Michigan will file a patent on THOR as a target and has filed a related technology disclosure around lncRNAs diagnostics in cancer. A.M.C., Y.H., and Y.S.N. will be named co-inventors. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = dec,
day = "14",
doi = "10.1016/j.cell.2017.11.040",
language = "English",
volume = "171",
pages = "1559--1572.e20",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}