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ZNF367-induced transcriptional activation of KIF15 accelerates the progression of breast cancer.
International Journal of Biological Sciences ( IF 9.2 ) Pub Date : 2020-05-16 , DOI: 10.7150/ijbs.44204
Huijuan Zeng 1, 2 , Tianfu Li 1, 2 , Duanyang Zhai 1, 2 , Jiong Bi 2 , Xiaying Kuang 1 , Sihong Lu 1, 2 , Zhen Shan 1 , Ying Lin 1
Affiliation  

Breast cancer (BC) is one of the most common female cancers, and its incidence has been increasing in recent years. Although treatments are continuously improving, the prognosis of patients in the advanced stage is still unsatisfactory. Thus, an in-depth understanding of its molecular mechanisms is necessary for curing breast cancer. KIF15 is a tetrameric spindle motor which can regulate mitosis in cellular process and exert the crucial functions in several cancers. The purpose of our research was to investigate the functions of KIF15 in breast cancer. We tested the expression of KIF15 in breast cancer tissues and the survival rate of breast cancer patients with high or low level of KIF15 through TCGA data. What's more, western blot and immunohistochemistry assay were utilized to evaluate the protein level and mRNA level of KIF15 in breast cancer tissues. Then CCK-8, wound healing, transwell and flow cytometry experiments were adopted separately to test cell viability, migration, invasion and cell cycle distribution. We discovered that KIF15 was highly expressed in breast cancer tissues and high level KIF15 was associated with a low survival rate of breast cancer patients. Moreover, silence of KIF15 suppressed cell viability, migration, invasion and cell cycle distribution. Following, we discovered that ZNF367 was the upstream transcription factor of KIF15. In addition, silenced ZNF367 could also repress the growth of breast cancer cells. And rescue experiments indicated that overexpressed KIF15 could counteract the inhibition effect of silencing ZNF367 on the progression of breast cancer. Importantly, we discovered that KIF15 and ZNF367 were associated with the regulation of cell cycle. In short, ZNF367-activated KIF15 accelerated the progression of breast cancer by regulating cell cycle progress.

中文翻译:

ZNF367 诱导的 KIF15 转录激活加速了乳腺癌的进展。

乳腺癌(BC)是女性最常见的癌症之一,近年来其发病率呈上升趋势。尽管治疗方法不断改进,但晚期患者的预后仍不理想。因此,深入了解其分子机制对于治疗乳腺癌是必要的。KIF15 是一种四聚体纺锤体马达,可以调节细胞过程中的有丝分裂,并在多种癌症中发挥关键作用。我们研究的目的是研究 KIF15 在乳腺癌中的功能。我们通过TCGA数据检测了KIF15在乳腺癌组织中的表达情况以及KIF15高或低水平的乳腺癌患者的生存率。更重要的是,采用蛋白质印迹法和免疫组化法检测乳腺癌组织中KIF15的蛋白水平和mRNA水平。然后分别采用CCK-8、伤口愈合、Transwell和流式细胞术实验来测试细胞活力、迁移、侵袭和细胞周期分布。我们发现 KIF15 在乳腺癌组织中高表达,高水平的 KIF15 与乳腺癌患者的低存活率有关。此外,KIF15 的沉默抑制了细胞活力、迁移、侵袭和细胞周期分布。随后,我们发现 ZNF367 是 KIF15 的上游转录因子。此外,沉默的 ZNF367 还可以抑制乳腺癌细胞的生长。并且救援实验表明,过表达的KIF15可以抵消沉默ZNF367对乳腺癌进展的抑制作用。重要的是,我们发现 KIF15 和 ZNF367 与细胞周期的调节有关。简而言之,ZNF367 激活的 KIF15 通过调节细胞周期进程加速了乳腺癌的进程。
更新日期:2020-05-16
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