Downregulation of KIF23 suppresses glioma proliferation

Satoshi Takahashi, Noemi Fusaki, Shigeki Ota, Yoshihiro Iwahori, Yukihiko Iizuka, Kohei Inagawa, Yutaka Kawakami, Kazunari Yoshida, Masahiro Toda

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

To identify therapeutic molecular targets for glioma, we performed modified serological identification of antigens by recombinant complementary DNA (cDNA) expression cloning using sera from a mouse glioma model. Two clones, kinesin family member 23 (Kif23) and structural maintenance of chromosomes 4 (Smc4), were identified as antigens through immunological reaction with sera from mice harboring synergic GL261 mouse glioma and intratumoral inoculation with a mutant herpes simplex virus. The human Kif23 homolog KIF23 is a nuclear protein that localizes to the interzone of mitotic spindles, acting as a plus-end-directed motor enzyme that moves antiparallel microtubules in vitro. Expression analysis revealed a higher level of KIF23 expression in glioma tissues than in normal brain tissue. The introduction of small interfering RNA (siRNA) targeting KIF23 into two different glioma cell lines, U87MG and SF126, downregulated KIF23 expression, which significantly suppressed glioma cell proliferation in vitro. KIF23 siRNA-treated glioma cells exhibited larger cell bodies with two or more nuclei compared with control cells. In vivo analysis using mouse xenograft showed that KIF23 siRNA/DNA chimeratreated tumors were significantly smaller than tumors treated with control siRNA/DNA chimera. Taken together, our results indicate that downregulation of KIF23 decreases proliferation of glioma cells and that KIF23 may be a novel therapeutic target in malignant glioma.

Original languageEnglish
Pages (from-to)519-529
Number of pages11
JournalJournal of Neuro-Oncology
Volume106
Issue number3
DOIs
Publication statusPublished - 2012 Feb

Fingerprint

Glioma
Down-Regulation
Small Interfering RNA
Kinesin
Cell Proliferation
Antigens
Chromosomes, Human, Pair 4
Spindle Apparatus
Recombinant DNA
DNA
Simplexvirus
Nuclear Proteins
Serum
Heterografts
Microtubules
Organism Cloning
Neoplasms
Complementary DNA
Clone Cells
Maintenance

Keywords

  • Glioma proliferation
  • KIF23
  • Microtube
  • MKLP1

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Cite this

Downregulation of KIF23 suppresses glioma proliferation. / Takahashi, Satoshi; Fusaki, Noemi; Ota, Shigeki; Iwahori, Yoshihiro; Iizuka, Yukihiko; Inagawa, Kohei; Kawakami, Yutaka; Yoshida, Kazunari; Toda, Masahiro.

In: Journal of Neuro-Oncology, Vol. 106, No. 3, 02.2012, p. 519-529.

Research output: Contribution to journalArticle

Takahashi, Satoshi ; Fusaki, Noemi ; Ota, Shigeki ; Iwahori, Yoshihiro ; Iizuka, Yukihiko ; Inagawa, Kohei ; Kawakami, Yutaka ; Yoshida, Kazunari ; Toda, Masahiro. / Downregulation of KIF23 suppresses glioma proliferation. In: Journal of Neuro-Oncology. 2012 ; Vol. 106, No. 3. pp. 519-529.
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