Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, Xiamen, China.
Department of Breast Surgery, Zhuhai Maternity and Child Health Hospital, Zhuhai, China.
Cancer Res Treat. 2019 Jul;51(3):1207-1221. doi: 10.4143/crt.2018.460. Epub 2018 Dec 27.
The study aimed to search and identify genes that were differentially expressed in breast cancer, and their roles in cancer growth and progression.
The Gene Expression Omnibus (Oncomine) and The Cancer Genome Atlas databases (https://cancergenome.nih.gov/) were screened for genes that were expressed differentially in breast cancer and were closely related to a poor prognosis. Gene expressions were verified by quantitative real-time polymerase chain reaction, and genes were knocked down by a lentivirus-based system. Cell growth and motility were evaluated and in vivo nude mice were used to confirm the in vitro roles of genes. Markers of epithelial-to-mesenchymal transition and the associations of KIF11 with the classical cancer signaling pathways were detected by Western blot.
A series of genes expressed differentially in patients with breast cancer. The prognosis associated with high KIF11 expression was poor, and the expression of KIF11 increased significantly in high stage and malignant tumor cells. Inhibiting KIF11 expression in lentivirus-suppressed cells revealed that KIF11 inhibition significantly reduced cell viability and colony formation, inhibited migration and invasion, but promoted apoptosis. The sizes and weights of KIF11-inhibited tumors in nude mice were significantly lower than in the negative controls. Western blot showed that E-cadherin in breast cancer was significantly upregulated in KIF-inhibited cells and tumor tissues, whereas N-cadherin and vimentin were significantly downregulated. BT549 and MDA231 cells with KIF11 knockdown exhibited decreased ERK, AMPK, AKT, and CREB phosphorylation.
KIF11 acts as a potential oncogene that regulates the development and progression of breast cancer.
本研究旨在搜索和鉴定在乳腺癌中差异表达的基因及其在癌症生长和进展中的作用。
通过基因表达综合数据库（Oncomine）和癌症基因组图谱数据库（https://cancergenome.nih.gov/）筛选出在乳腺癌中表达差异且与预后不良密切相关的基因。通过实时定量聚合酶链反应验证基因表达，并通过基于慢病毒的系统敲低基因。评估细胞生长和迁移，并在体内裸鼠中验证基因的体外作用。通过 Western blot 检测上皮间质转化标志物和 KIF11 与经典癌症信号通路的关联。
一系列在乳腺癌患者中差异表达的基因。与高 KIF11 表达相关的预后较差，并且在高分期和恶性肿瘤细胞中 KIF11 的表达显著增加。在慢病毒抑制的细胞中抑制 KIF11 表达表明，KIF11 抑制显著降低细胞活力和集落形成，抑制迁移和侵袭，但促进凋亡。裸鼠中 KIF11 抑制肿瘤的大小和重量明显低于阴性对照。Western blot 显示，KIF 抑制细胞和肿瘤组织中乳腺癌的 E-钙黏蛋白明显上调，而 N-钙黏蛋白和波形蛋白明显下调。BT549 和 MDA231 细胞中 KIF11 的敲低导致 ERK、AMPK、AKT 和 CREB 磷酸化减少。
KIF11 作为一种潜在的癌基因，调节乳腺癌的发生和发展。
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