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

H. J. Kwak, Y. J. Kim, K. R. Chun, Y. M. Woo, S. J. Park, J. A. Jeong, S. H. Jo, T. H. Kim, H. S. Min, J. S. Chae, Eui Ju Choi, G. Kim, S. H. Shin, H. S. Gwak, S. K. Kim, E. K. Hong, G. K. Lee, K. H. Choi, J. H. Kim, H. YooJ. B. Park, S. H. Lee

Research output: Contribution to journalArticle

88 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2433-2442
Number of pages10
JournalOncogene
Volume30
Issue number21
DOIs
Publication statusPublished - 2011 May 26

Fingerprint

Glioma
Down-Regulation
Neoplasms
MicroRNAs
Phosphoric Monoester Hydrolases
Hyaluronic Acid
Intercellular Signaling Peptides and Proteins
Proteins
Up-Regulation
Messenger RNA
Mortality

Keywords

  • glioma
  • hyaluronan
  • invasion
  • miR-21
  • PTEN
  • spry2

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Kwak, H. J., Kim, Y. J., Chun, K. R., Woo, Y. M., Park, S. J., Jeong, J. A., ... Lee, S. H. (2011). Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. Oncogene, 30(21), 2433-2442. https://doi.org/10.1038/onc.2010.620

Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. / Kwak, H. J.; Kim, Y. J.; Chun, K. R.; Woo, Y. M.; Park, S. J.; Jeong, J. A.; Jo, S. H.; Kim, T. H.; Min, H. S.; Chae, J. S.; Choi, Eui Ju; Kim, G.; Shin, S. H.; Gwak, H. S.; Kim, S. K.; Hong, E. K.; Lee, G. K.; Choi, K. H.; Kim, J. H.; Yoo, H.; Park, J. B.; Lee, S. H.

In: Oncogene, Vol. 30, No. 21, 26.05.2011, p. 2433-2442.

Research output: Contribution to journalArticle

Kwak, HJ, Kim, YJ, Chun, KR, Woo, YM, Park, SJ, Jeong, JA, Jo, SH, Kim, TH, Min, HS, Chae, JS, Choi, EJ, Kim, G, Shin, SH, Gwak, HS, Kim, SK, Hong, EK, Lee, GK, Choi, KH, Kim, JH, Yoo, H, Park, JB & Lee, SH 2011, 'Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas', Oncogene, vol. 30, no. 21, pp. 2433-2442. https://doi.org/10.1038/onc.2010.620
Kwak HJ, Kim YJ, Chun KR, Woo YM, Park SJ, Jeong JA et al. Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. Oncogene. 2011 May 26;30(21):2433-2442. https://doi.org/10.1038/onc.2010.620
Kwak, H. J. ; Kim, Y. J. ; Chun, K. R. ; Woo, Y. M. ; Park, S. J. ; Jeong, J. A. ; Jo, S. H. ; Kim, T. H. ; Min, H. S. ; Chae, J. S. ; Choi, Eui Ju ; Kim, G. ; Shin, S. H. ; Gwak, H. S. ; Kim, S. K. ; Hong, E. K. ; Lee, G. K. ; Choi, K. H. ; Kim, J. H. ; Yoo, H. ; Park, J. B. ; Lee, S. H. / Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. In: Oncogene. 2011 ; Vol. 30, No. 21. pp. 2433-2442.
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