title: Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis.
abstract: Accumulating studies have demonstrated the importance of long noncoding RNAs (lncRNAs) during oncogenic transformation. However, because most lncRNAs are currently uncharacterized, the identification of novel oncogenic lncRNAs is difficult. Given that intergenic lncRNA have substantially less sequence conservation patterns than protein-coding genes across species, evolutionary conserved intergenic lncRNAs are likely to be functional. The current study identified a novel intergenic lncRNA, LINC00461 (ECONEXIN) using a combined approach consisting of searching lncRNAs by evolutionary conservation and validating their expression in a glioma mouse model. ECONEXIN was the most highly conserved intergenic lncRNA containing 83.0% homology with the mouse ortholog (C130071C03Rik) for a region over 2500 bp in length within its exon 3. Expressions of ECONEXIN and C130071C03Rik were significantly upregulated in both human and mouse glioma tissues. Moreover, the expression of C130071C03Rik was upregulated even in precancerous conditions and markedly increased during glioma progression. Functional analysis of ECONEXIN in glioma cell lines, U87 and U251, showed it was dominantly located in the cytoplasm and interacted with miR-411-5p via two binding sites within ECONEXIN. Inhibition of ECONEXIN upregulated miR-411-5p together with the downregulation of its target, Topoisomerase 2 alpha (TOP2A), in glioma cell lines, resulting in decreased cell proliferation. Our data demonstrated that ECONEXIN is a potential oncogene that regulates TOP2A by sponging miR-411-5p in glioma. In addition, our investigative approaches to identify conserved lncRNA and their molecular characterization by validation in mouse tumor models may be useful to functionally annotate novel lncRNAs, especially cancer-associated lncRNAs.
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.|Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Deguchi
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Katsushima
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hatanaka
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shinjo
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Ohka
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Wakabayashi
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors.forename: H
authors.identifier: 0000-0002-4263-9633
authors.initials: H
authors.lastname: Zong
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Natsume
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017124:Conserved Sequence; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009857:Oncogenes; D000075223:Poly-ADP-Ribose Binding Proteins; D011230:Precancerous Conditions / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C000622833:LINC00461 lncRNA, human; C582326:MIRN411 microRNA, human; D035683:MicroRNAs; D000075223:Poly-ADP-Ribose Binding Proteins; D062085:RNA, Long Noncoding; D034743:RNA-Induced Silencing Complex; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; C000618812:Top2a protein, mouse