The Department of Breast Surgery, The Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, PR China.
The Department of Breast Surgery, The Tumor Hospital of XuZhou, XuZhou, JiangSu Province, PR China.
Mol Carcinog. 2019 Jun;58(6):933-943. doi: 10.1002/mc.22982. Epub 2019 Feb 22.
NEK5, a contraction of NIMA Related Kinase 5, has been shown to regulate the centrosome integrity of cells though; it has been little described in cancer. Herein, to explore the clinicopathological meaning of NEK5 expression in breast cancer, immunohistochemistry was performed to detect the expression of NEK5 on tissue blocks, totaling 203 cases. Quantitative real-time PCR (qRT-PCR) was used to evaluate NEK5 mRNA expression with 30 cases of fresh tissues. To observe the function of NEK5 in the growth of breast cancer cells, both MTT and xenografted nude mice were performed. And Transwell assay was employed to observe the variation of migration and invasion. It was shown that up-regulated NEK5 was significantly associated with tumor progression and poor overall prognosis; and that silencing of NEK5 can significantly suppress the proliferation both in vivo and in vitro, inhibiting migration, and invasion. To get insight into the underlying mechanism by which NEK5 operates in proliferation of breast cancer cells, we showed that NEK5 can up-regulate Cyclin A2 and down-regulate Cyclin D1, Cyclin D3, and Cyclin E1 expression. Additionally, Cyclin A2 was also identified as a novel interacting protein for NEK5. Taking together, we firstly defined the oncogenic role of NEK5 in breast cancer that was related to proliferation, supporting that NEK5 might be used a new therapeutic target in breast cancer.
NIMA 相关激酶 5(NEK5)可调节细胞中心体的完整性,但在癌症中描述较少。在此,通过免疫组织化学检测 203 例组织块中 NEK5 的表达,探讨 NEK5 表达在乳腺癌中的临床病理意义。采用定量实时 PCR(qRT-PCR)检测 30 例新鲜组织中 NEK5 mRNA 的表达。为观察 NEK5 在乳腺癌细胞生长中的功能,进行了 MTT 和异种移植裸鼠实验,并采用 Transwell 实验观察迁移和侵袭的变化。结果表明,上调的 NEK5 与肿瘤进展和整体预后不良显著相关;沉默 NEK5 可显著抑制体内外增殖,抑制迁移和侵袭。为了深入了解 NEK5 在乳腺癌细胞增殖中的作用机制,我们发现 NEK5 可以上调细胞周期蛋白 A2,下调细胞周期蛋白 D1、D3 和 E1 的表达。此外,细胞周期蛋白 A2 也被鉴定为 NEK5 的一种新型相互作用蛋白。综上所述,我们首次定义了 NEK5 在乳腺癌中的致癌作用与增殖有关,支持 NEK5 可能成为乳腺癌的新治疗靶点。