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A miR-21 inhibitor enhances apoptosis and reduces G2-M accumulation induced by ionizing radiation in human glioblastoma U251 cells

Brain Tumor Pathology volume 28, pages 209–214 (2011)Cite this article

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that take part in diverse biological processes by suppressing target gene expression. Elevated expression of miR-21 has been reported in many types of human cancers. Radiotherapy is a standard adjuvant treatment for patients with glioblastoma. However, the resistance of glioblastoma cells to radiation limits the success of this treatment. In this study, we found that miR-21 expression was upregulated in response to ionizing radiation (IR) in U251 cells, which suggested that miR-21 could be involved in the response of U251 cells to radiation. We showed that a miR-21 inhibitor enhanced IR-induced glioblastoma cell growth arrest and increased the level of apoptosis, which was probably caused by abrogation of the G2-M arrest induced by IR. Further research demonstrated that the miR-21 inhibitor induced the upregulation of Cdc25A. Taken together, these findings suggest that miR-21 inhibitor can increase IR-induced growth arrest and apoptosis in U251 glioblastoma cells, at least in part by abrogating G2-M arrest, and that Cdc25A is a potential target of miR-21.

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Acknowledgments

The authors thank Dr. Runze Xun and Dr. Jingshan Lu for their excellent technical assistance.

Author information

Affiliations

  1. Department of Neurosurgery, Kansai Medical University, Moriguchi, Osaka, 570-8507, Japan

    Yi Li, Qiang Li, Akio Asai & Keiji Kawamoto

  2. Department of Neurosurgery, The First Clinical College of Harbin Medical University, Harbin, Heilongjiang, 150001, China

    Yi Li, Shiguang Zhao, Yunbo Zhen & Lei Teng

Authors
  1. Yi Li
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  2. Shiguang Zhao
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  3. Yunbo Zhen
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  4. Qiang Li
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  5. Lei Teng
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  6. Akio Asai
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  7. Keiji Kawamoto
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Corresponding author

Correspondence to Keiji Kawamoto.

Additional information

Y. Li and S. Zhao contributed equally to this work.

Electronic supplementary material

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10014_2011_37_MOESM1_ESM.tif

Additional Fig. 1. When DNA is damaged by radiation (IR), CHK1 is activated, and CHK1 then targets cell division cycle 25A (Cdc25A) to ubiquitin-mediated degradation. The CHK1-dependent degradation of Cdc25A is a major p53-independent mechanism of either cell-cycle arrest or a delay in the G2-M phase. Eventually, DNA damage results in cell-cycle arrest at G2-M. The G2 checkpoint has a protective function; therefore, the fate of the injured cells is determined by the extent of DNA damage and the duration of G2-M. The restored cells thereafter survive, whereas the unrestored cells undergo apoptosis (TIFF 38590 kb)

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Li, Y., Zhao, S., Zhen, Y. et al. A miR-21 inhibitor enhances apoptosis and reduces G2-M accumulation induced by ionizing radiation in human glioblastoma U251 cells. Brain Tumor Pathol 28, 209–214 (2011). https://doi.org/10.1007/s10014-011-0037-1

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  • DOI: https://doi.org/10.1007/s10014-011-0037-1

Keywords

  • Glioblastoma
  • MiR-21
  • Ionizing radiation
  • Cdc25A
  • Cell cycle