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Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA.
Hosono, Yasuyuki; Niknafs, Yashar S; Prensner, John R; Iyer, Matthew K; Dhanasekaran, Saravana M; Mehra, Rohit; Pitchiaya, Sethuramasundaram; Tien, Jean; Escara-Wilke, June; Poliakov, Anton; Chu, Shih-Chun; Saleh, Sahal; Sankar, Keerthana; Su, Fengyun; Guo, Shuling; Qiao, Yuanyuan; Freier, Susan M; Bui, Huynh-Hoa; Cao, Xuhong; Malik, Rohit; Johnson, Timothy M; Beer, David G; Feng, Felix Y; Zhou, Weibin; Chinnaiyan, Arul M.
Affiliation
  • Hosono Y; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Niknafs YS; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA.
  • Prensner JR; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
  • Iyer MK; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Dhanasekaran SM; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Mehra R; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Pitchiaya S; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Tien J; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Escara-Wilke J; Department of Urology, University of Michigan, Ann Arbor, MI, USA.
  • Poliakov A; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Chu SC; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Saleh S; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Sankar K; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Su F; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Guo S; Ionis Pharmaceuticals, Carlsbad, CA, USA.
  • Qiao Y; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Freier SM; Ionis Pharmaceuticals, Carlsbad, CA, USA.
  • Bui HH; Ionis Pharmaceuticals, Carlsbad, CA, USA.
  • Cao X; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Malik R; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Johnson TM; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
  • Beer DG; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Feng FY; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
  • Zhou W; Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
  • Chinnaiyan AM; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan,
Cell ; 171(7): 1559-1572.e20, 2017 Dec 14.
Article in En | MEDLINE | ID: mdl-29245011
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.
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Full text: 1 Database: MEDLINE Main subject: Zebrafish / Disease Models, Animal / RNA, Long Noncoding / Melanoma Limits: Animals / Humans / Male Language: En Year: 2017 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Zebrafish / Disease Models, Animal / RNA, Long Noncoding / Melanoma Limits: Animals / Humans / Male Language: En Year: 2017 Type: Article