DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating MIR-21 biogenesis

Jinlong Yin, Gunwoo Park, Jeong Eun Lee, Eun Young Choi, Ju Young Park, Tae Hoon Kim, Nayun Park, Xiong Jin, Ji Eun Jung, Daye Shin, Jun Hee Hong, Hyunggee Kim, Heon Yoo, Seung Hoon Lee, Youn Jae Kim, Jong Bae Park, Jong Heon Kim

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Upregulation of microRNA-21 (miR-21) is known to be strongly associated with the proliferation, invasion, and radio-resistance of glioma cells. However, the regulatory mechanism that governs the biogenesis of miR-21 in glioma is still unclear. Here, we demonstrate that the DEAD-box RNA helicase, DDX23, promotes miR-21 biogenesis at the post-transcriptional level. The expression of DDX23 was enhanced in glioma tissues compared to normal brain, and expression level of DDX23 was highly associated with poor survival of glioma patients. Specific knockdown of DDX23 expression suppressed glioma cell proliferation and invasion in vitro and in vivo, which is similar to the function of miR-21. We found that DDX23 increased the level of miR-21 by promoting primary-to-precursor processing of miR-21 through an interaction with the Drosha microprocessor. Mutagenesis experiments critically demonstrated that the helicase activity of DDX23 was essential for the processing (cropping) of miR-21, and we further found that ivermectin, a RNA helicase inhibitor, decreased miR-21 levels by potentially inhibiting DDX23 activity and blocked invasion and cell proliferation. Moreover, treatment of ivermectin decreased glioma growth in mouse xenografts. Taken together, these results suggest that DDX23 plays an essential role in glioma progression, and might thus be a potential novel target for the therapeutic treatment of glioma.

Original languageEnglish
Pages (from-to)2553-2570
Number of pages18
JournalBrain
Volume138
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1

Keywords

  • DDX23
  • glioma
  • MIR-21
  • miRNA biogenesis

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Yin, J., Park, G., Lee, J. E., Choi, E. Y., Park, J. Y., Kim, T. H., Park, N., Jin, X., Jung, J. E., Shin, D., Hong, J. H., Kim, H., Yoo, H., Lee, S. H., Kim, Y. J., Park, J. B., & Kim, J. H. (2015). DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating MIR-21 biogenesis. Brain, 138(9), 2553-2570. https://doi.org/10.1093/brain/awv167