KIAA0101 inhibition suppresses cell proliferation and cell cycle progression by promoting the interaction between p53 and Sp1 in breast cancer
KIAA0101 inhibition suppresses cell proliferation and cell cycle progression by promoting the interaction between p53 and Sp1 in breast cancer
复制标题
KIAA0101 抑制通过促进乳腺癌中 p53 和 Sp1 之间的相互作用来抑制细胞增殖和细胞周期进程
DOI：
10.1016/j.bbrc.2018.06.046
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发表时间：
2018-09-05
影响因子：
3.1
通讯作者：
Chen, Na
中科院分区：
文献类型：
--
作者：
Lv, Wei;Su, Benhua;Chen, Na
KIAA0101在乳腺癌中起着中心体数量的调节作用。在这里，我们确定了KIAA0101在乳腺癌细胞增殖和细胞周期进程中的作用。KIAA0101基因敲除可显著抑制细胞生长、集落形成和G1/S期转变。进一步的研究表明，KIAA0101沉默抑制了CCNE2、CDK6和CDKN1A的表达。荧光素酶报告实验和芯片实验表明，Sp1正向调控CCNE2、CDK6和CDKN1A的转录。KIAA0101基因敲除促进了P53和Sp1之间的相互作用，抑制了Sp1对CCNE2、CDK6和CDKN1A的转录激活。P53基因敲除抵消了KIAA0101基因敲除对乳腺癌细胞增殖和细胞周期进程的抑制作用，而Sp1基因敲除与KIAA0101基因敲除的作用相似。提示KIAA0101基因敲除通过促进P53/Sp1复合体的形成，抑制乳腺癌细胞增殖和细胞周期进程。(C)2018 Elsevier Inc.保留所有权利。
KIAA0101 functions as a regulator of centrosome number in breast cancer. Here, we identify the role of KIAA0101 in breast cancer cell proliferation and cell cycle progression. KIAA0101 knockdown significantly inhibited cell growth, colony formation and G1/S phase transition. Further investigation indicated that KIAA0101 silencing suppressed the expression of CCNE2, CDK6 and CDKN1A. Luciferase reporter assay and ChIP assay demonstrated that Sp1 positively regulated the transcription of CCNE2, CDK6 and CDKN1A. KIAA0101 knockdown promoted the interaction between p53 and Sp1, inhibiting the transcriptional activation of Sp1 on CCNE2, CDK6 and CDKN1A. Knockdown of p53 counteracted the inhibitory effect of KIAA0101 knockdown on breast cancer cells proliferation and cell cycle progression while Sp1 knockdown mimicked the effect of KIAA0101 knockdown. These results suggested that KIAA0101 knockdown suppressed the cell proliferation and cell cycle progression by promoting the formation of p53/Sp1 complex in breast cancer. (C) 2018 Elsevier Inc. All rights reserved.