Laboratory Investigation - Human/Animal Tissue

Journal of Neuro-Oncology

, Volume 106, Issue 3, pp 519-529

Downregulation of KIF23 suppresses glioma proliferation

  • Satoshi TakahashiAffiliated withDepartment of Neurosurgery, Keio University, School of Medicine
  • , Noemi FusakiAffiliated withNeuro-immunology Research Group, Keio University, School of Medicine
  • , Shigeki OhtaAffiliated withNeuro-immunology Research Group, Keio University, School of MedicineDivision of Cellular Signaling, Institute for Advanced Medical Research, Keio University, School of Medicine
  • , Yoshihiro IwahoriAffiliated withNeuro-immunology Research Group, Keio University, School of Medicine
  • , Yukihiko IizukaAffiliated withNeuro-immunology Research Group, Keio University, School of Medicine
  • , Kohei InagawaAffiliated withNeuro-immunology Research Group, Keio University, School of Medicine
  • , Yutaka KawakamiAffiliated withDivision of Cellular Signaling, Institute for Advanced Medical Research, Keio University, School of Medicine
  • , Kazunari YoshidaAffiliated withDepartment of Neurosurgery, Keio University, School of Medicine
  • , Masahiro TodaAffiliated withDepartment of Neurosurgery, Keio University, School of MedicineNeuro-immunology Research Group, Keio University, School of Medicine Email author 

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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 chimera-treated 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.

Keywords

Glioma proliferation KIF23 MKLP1 Microtube