Downregulation of KIF23 suppresses glioma proliferation
Downregulation of KIF23 suppresses glioma proliferation
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DOI：
10.1007/s11060-011-0706-2
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发表时间：
2012-02-01
影响因子：
3.9
通讯作者：
Toda, Masahiro
中科院分区：
文献类型：
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作者：
Takahashi, Satoshi;Fusaki, Noemi;Toda, Masahiro
为了确定胶质瘤的治疗分子靶点，我们利用小鼠脑胶质瘤模型的血清，通过重组互补DNA(CDNAs)的表达克隆，对抗原进行了改良的血清学鉴定。通过与GL261小鼠胶质瘤小鼠血清的免疫反应和瘤内接种突变的单纯疱疹病毒，鉴定了两个克隆：KIF23和SMC4，分别是KIF23和SMC4。人类KIF23同源物KIF23是一种核蛋白，定位于有丝分裂纺锤体的区间区，在体外作为正端定向的运动酶移动反平行微管。表达分析显示，KIF23在胶质瘤组织中的表达水平高于正常脑组织。将针对KIF23的小干扰RNA(SiRNA)导入两种不同的胶质瘤细胞系U87 MG和SF126中，可下调KIF23的表达，从而显著抑制胶质瘤细胞的体外增殖。与对照组相比，KIF23 siRNA处理的胶质瘤细胞显示出更大的胞体，有两个或更多的核。小鼠移植瘤体内分析表明，KIF23 siRNA/DNA嵌合体治疗的肿瘤明显小于对照siRNA/DNA嵌合体治疗的肿瘤。综上所述，我们的结果表明KIF23的下调抑制了胶质瘤细胞的增殖，KIF23可能是恶性胶质瘤的一个新的治疗靶点。
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.