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

20 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

Fingerprint

DEAD-box RNA Helicases
MicroRNAs
Glioma
Neoplasms
Ivermectin
Cell Proliferation
RNA Helicases
Microcomputers
Radio
Heterografts
Mutagenesis
Up-Regulation
Therapeutics

Keywords

  • DDX23
  • glioma
  • MIR-21
  • miRNA biogenesis

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Yin, J., Park, G., Lee, J. E., Choi, E. Y., Park, J. Y., Kim, T. H., ... 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

DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating MIR-21 biogenesis. / Yin, Jinlong; Park, Gunwoo; Lee, Jeong Eun; Choi, Eun Young; Park, Ju Young; Kim, Tae Hoon; Park, Nayun; Jin, Xiong; Jung, Ji Eun; Shin, Daye; Hong, Jun Hee; Kim, Hyunggee; Yoo, Heon; Lee, Seung Hoon; Kim, Youn Jae; Park, Jong Bae; Kim, Jong Heon.

In: Brain, Vol. 138, No. 9, 01.09.2015, p. 2553-2570.

Research output: Contribution to journalArticle

Yin, J, Park, G, Lee, JE, Choi, EY, Park, JY, Kim, TH, Park, N, Jin, X, Jung, JE, Shin, D, Hong, JH, Kim, H, Yoo, H, Lee, SH, Kim, YJ, Park, JB & Kim, JH 2015, 'DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating MIR-21 biogenesis', Brain, vol. 138, no. 9, pp. 2553-2570. https://doi.org/10.1093/brain/awv167
Yin J, Park G, Lee JE, Choi EY, Park JY, Kim TH et al. DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating MIR-21 biogenesis. Brain. 2015 Sep 1;138(9):2553-2570. https://doi.org/10.1093/brain/awv167
Yin, Jinlong ; Park, Gunwoo ; Lee, Jeong Eun ; Choi, Eun Young ; Park, Ju Young ; Kim, Tae Hoon ; Park, Nayun ; Jin, Xiong ; Jung, Ji Eun ; Shin, Daye ; Hong, Jun Hee ; Kim, Hyunggee ; Yoo, Heon ; Lee, Seung Hoon ; Kim, Youn Jae ; Park, Jong Bae ; Kim, Jong Heon. / DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating MIR-21 biogenesis. In: Brain. 2015 ; Vol. 138, No. 9. pp. 2553-2570.
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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.",
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AU - Park, Ju Young

AU - Kim, Tae Hoon

AU - Park, Nayun

AU - Jin, Xiong

AU - Jung, Ji Eun

AU - Shin, Daye

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AU - Kim, Hyunggee

AU - Yoo, Heon

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N2 - 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.

AB - 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.

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