Li Xishan, Huang Weimei, Huang Wenbin, Wei Ting, Zhu Weiliang, Chen Guodong, Zhang Jian
Department of Oncology, Zhujiang Hospital, Southern Medical University 253 Industrial Avenue, Guangzhou 510282, China.
Department of Interventional Radiology, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology No. 1 Panfu Road, Guangzhou 510180, China.
Am J Transl Res. 2020 May 15;12(5):1614-1639. eCollection 2020.
Kinesin superfamily proteins (KIFs) comprise a family of molecular motors that transport membranous organelles and protein complexes in a microtubule- and ATP-dependent manner, with multiple roles in cancers. Little is known about the function of KIFs in hepatocellular carcinoma (HCC). Here, we investigate the roles of KIFs in the prognosis and progression of HCC. Upregulation of eight KIFs (KIF2C, KIF4A, KIF10, KIF11, KIF14, KIF18B, KIF20A, and KIF23) was found to be significantly associated with the tumor stage and pathological tumor grade of HCC patients. Additionally, a high expression of these eight KIFs was significantly associated with shorter overall survival (OS) and disease-free survival (DFS) in patients with HCC. Cox regression analysis showed the mRNA expression levels of these eight KIF members to be independent prognostic factors for worse outcomes in HCC. Moreover, a risk score model based on the mRNA levels of the eight KIF members effectively predicted the OS rate of patients with HCC. Additional experiments revealed that downregulation of each of the eight KIFs effectively decreased the proliferation and increased the G1 arrest of liver cancer cells in vitro. Taken together, these results indicate that KIF2C/4A/10/11/14/18B/20A/23 may serve as prognostic biomarkers for survival and potential therapeutic targets in HCC patients.
驱动蛋白超家族蛋白(KIFs)是一类分子马达,以微管和ATP依赖的方式运输膜性细胞器和蛋白质复合物,在癌症中发挥多种作用。关于KIFs在肝细胞癌(HCC)中的功能知之甚少。在此,我们研究了KIFs在HCC预后和进展中的作用。发现8种KIFs(KIF2C、KIF4A、KIF10、KIF11、KIF14、KIF18B、KIF20A和KIF23)的上调与HCC患者的肿瘤分期和病理肿瘤分级显著相关。此外,这8种KIFs的高表达与HCC患者较短的总生存期(OS)和无病生存期(DFS)显著相关。Cox回归分析表明,这8种KIF成员的mRNA表达水平是HCC患者预后较差的独立预后因素。此外,基于这8种KIF成员mRNA水平的风险评分模型有效地预测了HCC患者的OS率。进一步的实验表明,下调这8种KIF中的每一种均可有效降低肝癌细胞的增殖并增加其在体外的G1期阻滞。综上所述,这些结果表明KIF2C/4A/10/11/14/18B/20A/23可能作为HCC患者生存的预后生物标志物和潜在的治疗靶点。