| Literature DB >> 29245011 |
Yasuyuki Hosono1, Yashar S Niknafs2, John R Prensner3, Matthew K Iyer4, Saravana M Dhanasekaran5, Rohit Mehra5, Sethuramasundaram Pitchiaya1, Jean Tien1, June Escara-Wilke6, Anton Poliakov1, Shih-Chun Chu1, Sahal Saleh1, Keerthana Sankar1, Fengyun Su1, Shuling Guo7, Yuanyuan Qiao1, Susan M Freier7, Huynh-Hoa Bui7, Xuhong Cao1, Rohit Malik5, Timothy M Johnson8, David G Beer9, Felix Y Feng10, Weibin Zhou11, Arul M Chinnaiyan12.
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.Entities:
Keywords: IGF2BP1; RNA; RNA-seq; cancer; conservation; fertility; iCLIP; lncRNA; zebrafish
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Year: 2017 PMID: 29245011 PMCID: PMC5734106 DOI: 10.1016/j.cell.2017.11.040
Source DB: PubMed Journal: Cell ISSN: 0092-8674 Impact factor: 41.582