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A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells

  • Research Article
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Tumor Biology

Abstract

Growing number of long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer origination and progression. A lncRNA, ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2), with unknown function, is the antisense transcript of tumor suppressor ADAMTS9. In the present study, we investigated the expression pattern and functional role of ADAMTS9-AS2 in glioma by using real-time PCR and gain-/loss-of-function studies. The results showed that the ADAMTS9-AS2 expression was significantly downregulated in tumor tissues compared with normal tissues and reversely associated with tumor grade and prognosis. Multivariate analysis of the prognosis factors showed that low ADAMTS9-AS2 expression was a significant independent predictor of poor survival in glioma. Overexpression of ADAMTS9-AS2 resulted in significant inhibition of cell migration in glioma, whereas knockdown of ADAMTS9-AS2 showed the opposite effect. We also found that ADAMTS9-AS2 expression was negatively correlated with DNA methyltransferase-1 (DNMT1). In addition, DNMT1 knockdown led to remarkable enhancement of ADAMTS9-AS2 expression. By 5-aza-dC treatment, the ADAMTS9-AS2 expression was also reactivated. The results suggested that ADAMTS9-AS2 is a novel tumor suppressor modulated by DNMT1 in glioma. LncRNA ADAMTS9-AS2 may serve as a potential biomarker and therapeutic target for glioma.

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Author information

Authors and Affiliations

  1. Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, 100048, China

    Jie Yao, Peiliang Geng & Yunfeng Zhu

  2. Department of Oncology, The 161th Hospital of PLA, Jiangan District, Wuhan, 430010, Hubei Province, China

    Jie Yao

  3. Department of Neurosurgery, The First Central Hospital of Tianjin, 56 Fukang Road, Tianjin, 300192, China

    Baosheng Zhou

  4. Department of Pathology, People’s Hospital of Binzhou, Binzhou, Shandong Province, China

    Jian Zhang

  5. Neurosurgery Department, Chinese PLA General Hospital, Jinan Military Command, Jinan, China

    Kang Liu & Weijie Zhu

  6. Department of Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100853, China

    Weijie Zhu

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  1. Jie Yao
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  4. Peiliang Geng
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Correspondence to Yunfeng Zhu or Weijie Zhu.

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Jie Yao, Baosheng Zhou, Jian Zhang, and Peiliang Geng are co-first author

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Yao, J., Zhou, B., Zhang, J. et al. A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells. Tumor Biol. 35, 7935–7944 (2014). https://doi.org/10.1007/s13277-014-1949-2

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  • DOI: https://doi.org/10.1007/s13277-014-1949-2

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