Qiao Yuan, Chen Jingtao, Ma Chao, Liu Yingmin, Li Peitong, Wang Yalin, Hou Lin, Liu Ziling
Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
Cancer Center, The First Hospital of Jilin University, Changchun, China.
Cell Physiol Biochem. 2018;51(1):1-10. doi: 10.1159/000495155. Epub 2018 Nov 15.
BACKGROUND/AIMS: Lung cancer is the leading cause of cancer-related deaths worldwide. The outcome of patients with non-small cell lung cancer remains poor; the 5-year survival rate for stage IV non-small cell lung cancer is only 1.0%. KIF15 is a tetrameric kinesin spindle motor that has been investigated for its regulation of mitosis. While the roles of kinesin motor proteins in the regulation of mitosis and their potentials as therapeutic targets in pancreatic cancer have been described previously, the role of KIF15 in lung cancer development remains unknown.
Paired lung carcinoma specimens and matched adjacent normal tissues were used for protein analysis. Clinical data were obtained from medical records. We first examined KIF15 messenger RNA expression in The Cancer Genome Atlas database, and then determined KIF15 protein levels using immunohistochemistry and western blotting. Differences between the groups were analyzed using repeated measures analysis of variance. Overall survival was analyzed using the Kaplan-Meier method. Cell-cycle and proliferation assays were conducted using A549, NCI-H1299, and NCI-H226 cells.
KIF15 was significantly upregulated at both the messenger RNA and protein levels in human lung tumor tissues. In patients with lung adenocarcinoma, KIF15 expression was positively associated with disease stages; high KIF15 expression predicted a poor prognosis. KIF15 knockdown using short hairpin RNA in two human lung adenocarcinoma cell lines induced G1/S phase cell cycle arrest and inhibited cell growth, but there was no effect in human lung squamous cell carcinoma.
Our findings show that KIF15 is involved in lung cancer carcinogenesis. KIF15 could therefore serve as a specific prognostic marker for patients with lung adenocarcinoma.
背景/目的：肺癌是全球癌症相关死亡的主要原因。非小细胞肺癌患者的预后仍然很差；IV期非小细胞肺癌的5年生存率仅为1.0%。KIF15是一种四聚体驱动蛋白纺锤体马达，其对有丝分裂的调节作用已得到研究。虽然此前已描述了驱动蛋白马达蛋白在有丝分裂调节中的作用及其作为胰腺癌治疗靶点的潜力，但KIF15在肺癌发生中的作用尚不清楚。
配对的肺癌标本和匹配的相邻正常组织用于蛋白质分析。临床数据从病历中获取。我们首先在癌症基因组图谱数据库中检测KIF15信使核糖核酸表达，然后使用免疫组织化学和蛋白质印迹法测定KIF15蛋白水平。使用重复测量方差分析来分析组间差异。使用Kaplan-Meier方法分析总生存期。使用A549、NCI-H1299和NCI-H226细胞进行细胞周期和增殖试验。
KIF15在人肺肿瘤组织中的信使核糖核酸和蛋白水平均显著上调。在肺腺癌患者中，KIFl5表达与疾病分期呈正相关；KIF15高表达预示着预后不良。在两个人肺腺癌细胞系中使用短发夹核糖核酸敲低KIF15可诱导G1/S期细胞周期停滞并抑制细胞生长，但对人肺鳞状细胞癌没有影响。
我们的研究结果表明KIF15参与肺癌的发生。因此，KIF15可以作为肺腺癌患者的特异性预后标志物。
