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Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis

Oncogene volume 36, pages 4629–4640 (2017)Cite this article

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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.

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Acknowledgements

This study was performed as research programs of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan (YK), of the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and development, AMED (YK), of the PRESTO, JST (YK) and of the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science (25290048, YK).

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Authors and Affiliations

  1. Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    S Deguchi, K Katsushima, A Hatanaka, K Shinjo & Y Kondo

  2. Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan

    S Deguchi, F Ohka, T Wakabayashi & A Natsume

  3. Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA

    H Zong

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  1. S Deguchi
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Correspondence to Y Kondo.

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Deguchi, S., Katsushima, K., Hatanaka, A. et al. Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis. Oncogene 36, 4629–4640 (2017). https://doi.org/10.1038/onc.2017.88

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