Silencing TTK expression inhibits the proliferation and progression of prostate cancer
Silencing TTK expression inhibits the proliferation and progression of prostate cancer
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DOI：
10.1016/j.yexcr.2019.111669
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发表时间：
2019-12-01
影响因子：
3.7
通讯作者：
Yang, Kuo
中科院分区：
文献类型：
--
作者：
Chen, Saipeng;Wang, Jianan;Yang, Kuo
目的：本研究的主要目的是探讨与前列腺癌进展相关的差异表达基因表达水平的变化，并设计一系列实验验证差异表达基因的功能。选择与Gleason评分相关的差异基因，并通过p0.3过滤掉< 0.05 and spearman coefficient >。KEGG信号通路丰富了差异表达的基因，选择TTK作为研究对象。在前列腺癌组织和前列腺癌细胞系中检测TTK的表达。结果TTK的表达与前列腺癌的Gleason评分呈正相关，在转移性前列腺癌细胞系中蛋白和mRNA的表达均高于非转移性前列腺癌细胞系。体外生物学实验表明，TTK基因敲除可抑制PC3和DU 145细胞的增殖、侵袭和迁移，促进细胞凋亡。体内实验表明，TTK敲除抑制小鼠肿瘤发生。结论：TTK是PCa恶性肿瘤的相关基因，TTK基因敲除后，PCa中CDK2和CCNE1的表达明显降低，提示TTK基因可能是PCa恶性肿瘤的一个新的治疗靶点。
Purpose: The main objective of our study was to explore changes in the expression levels of differentially expressed genes associated with prostate cancer progression and to design a series of experiments to verify the function of differentially expressed genes.Method: The transcriptome datas of 499 cases of prostate cancer patients was downloaded from TCGA database. Differential genes associated with Gleason score were selected and filtered out by p < 0.05 and spearman coefficient > 0.3. KEGG signaling pathway was enriched by differentially expressed genes, and TTK was selected as the research object. The expression of TTK was tested in prostate cancer tissues and prostate cancer cell lines. The changes of biological behavior of prostate cancer cell lines were verified after UK was knocked out by siRNA and tumorigenic effect of TTK was verified by shRNA in vivo experiments.Result The expression of TTK was positively correlated with Gleason score of prostate cancer, and the expression of protein and mRNA in metastatic prostate cancer cell lines was higher than that in non-metastatic prostate cancer cell lines. Vitro biological experiments showed that TTK gene knockout could inhibit the proliferation, invasion and migration of PC3 and DU145 cells, and promote cell apoptosis. In vivo experiments showed that TTK knockout inhibited tumorigenesis in mice. It was found that the expression of CDK2 and CCNE1 decreased after TTK was knocked out.Conclusion: Our results suggest that TTK is a gene associated with malignancy of PCa and could be a novel therapeutic target for clinical application.