RRC ID 50504
Author Deguchi S, Katsushima K, Hatanaka A, Shinjo K, Ohka F, Wakabayashi T, Zong H, Natsume A, Kondo Y.
Title Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis.
Journal Oncogene
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.
Volume 36(32)
Pages 4629-4640
Published 2017-8-10
DOI 10.1038/onc.2017.88
PII onc201788
PMID 28368417
MeSH Animals Antigens, Neoplasm / metabolism* Brain Neoplasms / genetics Brain Neoplasms / metabolism* Carcinogenesis / genetics* Cell Line, Tumor Cell Proliferation Conserved Sequence DNA Topoisomerases, Type II / metabolism* DNA-Binding Proteins / metabolism* Disease Progression Down-Regulation Glioma / genetics Glioma / metabolism* Humans Mice MicroRNAs / metabolism* Oncogenes* Poly-ADP-Ribose Binding Proteins Precancerous Conditions / genetics RNA, Long Noncoding / genetics RNA, Long Noncoding / metabolism* RNA-Induced Silencing Complex / metabolism Up-Regulation
IF 7.971
Times Cited 29
DNA material p3xFLAG-Myc-CMV-AGO2-WT (RDB15797) p3xFLAG-Myc-CMV-AGO2-PAZ-mut (RDB15798) p3xFLAG-Myc-CMV-AGO2-PAZ-del (RDB15799) pmirGLO-TOP2A-3'-UTR (RDB15800) pcDNA-DEST47-TOP2A (RDB15801).