title: DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis.
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.
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Yin
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Gunwoo
authors.initials: G
authors.lastname: Park
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 3 Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 3 Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 3 Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Nayun
authors.initials: N
authors.lastname: Park
authors.affiliation: 4 Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Xiong
authors.initials: X
authors.lastname: Jin
authors.affiliation: 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 4 Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Jung
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 3 Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Daye
authors.initials: D
authors.lastname: Shin
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Hong
authors.affiliation: 4 Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Heon
authors.initials: H
authors.lastname: Yoo
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 2 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Jong Bae
authors.initials: JB
authors.lastname: Park
authors.affiliation: 1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 3 Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea jhkim@ncc.re.kr jbp@ncc.re.kr yjkim@ncc.re.kr.
authors.forename: Jong Heon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D007559:Ivermectin / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000977:Antiparasitic Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007559:Ivermectin; C498290:DDX23 protein, human; D053487:DEAD-box RNA Helicases
keywords: DDX23; glioma; miR-21; miRNA biogenesis