Department of Comprehensive Liver Cancer, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of General Surgery, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
J Cell Physiol. 2020 Oct;235(10):6507-6514. doi: 10.1002/jcp.29444. Epub 2020 Feb 13.
This study aimed to investigate the functional roles of kinesin family member 18B (KIF18B) in hepatocellular carcinoma (HCC) development, as well as the related molecular mechanisms. Tissue specimens were collected from 105 patients with HCC, and the messenger RNA (mRNA) and protein levels of KIF18B were detected using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The χ test was performed to estimate the association of KIF18B with clinical characteristics of patients with HCC. Effects of KIF18B expression on biological behaviors of HCC cells were detected by clone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and transwell assays. The expression patterns of proteins were investigated using Western blot analysis. HCC tissues and cell lines showed significant upregulation of KIF18B at both mRNA and protein levels (p > .05, for all). Furthermore, the elevated KIF18B expression was positively correlated with the tumor-node-metastasis stage (p = .015) and lymph node metastasis (p = .007). Knockdown of KIF18B might suppress HCC cell clone formation, proliferation, migration, and invasion in vitro. Besides, the activity of Wnt/β-catenin pathway was also significantly inhibited after the KIF18B knockdown. However, the antitumor actions caused by KIF18B knockdown might be reversed by lithium chloride treatment, which was the inducer of Wnt/β-catenin-signaling pathway. KIF18B may serve as an oncogene in HCC through enhancing the activity of Wnt/β-catenin pathway.
本研究旨在探讨驱动蛋白家族成员 18B（KIF18B）在肝细胞癌（HCC）发展中的功能作用及其相关的分子机制。收集了 105 例 HCC 患者的组织标本，分别采用实时定量聚合酶链反应和免疫组织化学检测 KIF18B 的信使 RNA（mRNA）和蛋白水平。采用 χ 检验估计 KIF18B 与 HCC 患者临床特征的相关性。通过克隆形成、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和 Transwell 测定检测 KIF18B 表达对 HCC 细胞生物学行为的影响。采用 Western blot 分析检测蛋白表达模式。HCC 组织和细胞系在 mRNA 和蛋白水平均显示出明显的 KIF18B 上调（p > .05，均）。此外，升高的 KIF18B 表达与肿瘤-淋巴结-转移分期（p = .015）和淋巴结转移（p = .007）呈正相关。体外敲低 KIF18B 可能抑制 HCC 细胞克隆形成、增殖、迁移和侵袭。此外，KIF18B 敲低后 Wnt/β-catenin 通路的活性也明显受到抑制。然而，用 Wnt/β-catenin 信号通路的诱导剂氯化锂处理后，KIF18B 敲低引起的抗肿瘤作用可能被逆转。KIF18B 可能通过增强 Wnt/β-catenin 通路的活性在 HCC 中作为癌基因发挥作用。
