Wang Chengqin, Zhang Runze, Wang Xiao, Zheng Yan, Jia Huiqing, Li Haiyan, Wang Jin, Wang Ning, Xiang Fenggang, Li Yujun
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, China.
Front Oncol. 2021 Jan 19;10:597464. doi: 10.3389/fonc.2020.597464. eCollection 2020.
Breast cancer is the most common malignant tumors in women. Kinesin family member 3B (KIF3B) is a critical regulator in mitotic progression. The objective of this study was to explore the expression, regulation, and mechanism of KIF3B in 103 cases of breast cancer tissues, 35 metastatic lymph nodes and breast cancer cell lines, including MDA-MB-231, MDA-MB-453, T47D, and MCF-7. The results showed that KIF3B expression was up-regulated in breast cancer tissues and cell lines, and the expression level was correlated with tumor recurrence and lymph node metastasis, while knockdown of KIF3B suppressed cell proliferation, migration, and invasion both and . In addition, UALCAN analysis showed that KIF3B expression in breast cancer is increased, and the high expression of KIF3B in breast cancer is associated with poor prognosis. Furthermore, we found that silencing of KIF3B decreased the expression of Dvl2, phospho-GSK-3, total and nucleus -catenin, then subsequent down-regulation of Wnt/-catenin signaling target genes such as CyclinD1, C-myc, MMP-2, MMP-7 and MMP-9 in breast cancer cells. In addition, KIF3B depletion inhibited epithelial mesenchymal transition (EMT) in breast cancer cells. Taken together, our results revealed that KIF3B is up-regulated in breast cancer which is potentially involved in breast cancer progression and metastasis. Silencing KIF3B might suppress the Wnt/-catenin signaling pathway and EMT in breast cancer cells.
乳腺癌是女性中最常见的恶性肿瘤。驱动蛋白家族成员3B（KIF3B）是有丝分裂进程中的关键调节因子。本研究的目的是探讨KIF3B在103例乳腺癌组织、35个转移淋巴结以及乳腺癌细胞系（包括MDA-MB-231、MDA-MB-453、T47D和MCF-7）中的表达、调控及其机制。结果显示，KIF3B在乳腺癌组织和细胞系中表达上调，其表达水平与肿瘤复发和淋巴结转移相关，而敲低KIF3B可抑制细胞增殖、迁移和侵袭。此外，UALCAN分析显示乳腺癌中KIF3B表达增加，且KIF3B在乳腺癌中的高表达与预后不良相关。此外，我们发现沉默KIF3B可降低Dvl2、磷酸化GSK-3、总β-连环蛋白和细胞核β-连环蛋白的表达，进而下调乳腺癌细胞中Wnt/β-连环蛋白信号通路的靶基因，如细胞周期蛋白D1、C-myc、基质金属蛋白酶-2、基质金属蛋白酶-7和基质金属蛋白酶-9。此外，KIF3B缺失抑制了乳腺癌细胞的上皮-间质转化（EMT）。综上所述，我们的结果表明KIF3B在乳腺癌中上调，可能参与乳腺癌的进展和转移。沉默KIF3B可能抑制乳腺癌细胞中的Wnt/β-连环蛋白信号通路和EMT。
