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  • Original Article
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Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas

Oncogene volume 30, pages 2433–2442 (2011)Cite this article

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Abstract

Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II–IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.

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Acknowledgements

This work was supported by the National Cancer Center Grants (1010171, 1010172, and 1110120) and the National Research Foundation Grant (2010-0016811). JHK was supported by the National Cancer Center Grant (1110110) and the National Research Foundation Grant (2010-0016704).

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Author notes

  1. H-J Kwak and Y-J Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea

    H-J Kwak, Y-J Kim, K-R Chun, Y M Woo, S-J Park, J-A Jeong, S H Jo, T H Kim, G Kim, K-H Choi & J B Park

  2. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea

    Y-J Kim

  3. Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang, Korea

    H S Min, E-K Hong & G-K Lee

  4. Laboratory of Cell Death and Human Diseases, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea

    J S Chae & E-J Choi

  5. Neuro-Oncology Clinic, Research Institute and Hospital, National Cancer Center, Goyang, Korea

    S-H Shin, H-S Gwak, H Yoo & S-H Lee

  6. Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea

    S-K Kim

  7. Carcinogenesis Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea

    J H Kim

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  1. H-J Kwak
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Correspondence to J B Park or S-H Lee.

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Kwak, HJ., Kim, YJ., Chun, KR. et al. Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. Oncogene 30, 2433–2442 (2011). https://doi.org/10.1038/onc.2010.620

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