E2F1 transcriptionally regulates CCNA2 expression to promote triple negative breast cancer tumorigenicity.

IF 1.9
Yongbin Lu, Fei Su, Hui Yang, Yi Xiao, Xiaobin Zhang, Hongxin Su, Tao Zhang, Yana Bai, Xiaoling Ling
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引用次数: 11

Abstract

Background: Triple-negative breast cancer (TNBC) is a highly malignant breast cancer subtype with a poor prognosis. The cell cycle regulator cyclin A2 (CCNA2) plays a role in tumor development. Herein, we explored the role of CCNA2 in TNBC.

Methods: We analyzed CCNA2 expression in 15 pairs of TNBC and adjacent tissues and assessed the relationship between CCNA2 expression using the tissue microarray cohort. Furthermore, we used two TNBC cohort datasets to analyze the correlation between CCNA2 and E2F transcription factor 1 (E2F1) and a luciferase reporter to explore their association. Through rescue experiments, we analyzed the effects of E2F1 knockdown on CCNA2 expression and cellular behavior.

Results: We found that CCNA2 expression in TNBC was significantly higher than that in adjacent tissues with similar observations in MDA-MB-231 and MDA-MB-468 cells. E2F1 was highly correlated with CCNA2 as observed through bioinformatics analysis (R= 0.80, P< 0.001) and through TNBC tissue verification analysis (R= 0.53, P< 0.001). We determined that E2F1 binds the +677 position within the CCNA2 promoter. Moreover, CCNA2 overexpression increased cell proliferation, invasion, and migration owing to E2F1 upregulation in TNBC.

Conclusion: Our data indicate that E2F1 promotes TNBC proliferation and invasion by upregulating CCNA2 expression. E2F1 and CCNA2 are potential candidates that may be targeted for effective TNBC treatment.

E2F1转录调控CCNA2表达促进三阴性乳腺癌的致瘤性。
背景:三阴性乳腺癌(TNBC)是一种预后较差的高度恶性乳腺癌亚型。细胞周期调节因子cyclin A2 (CCNA2)在肿瘤发展中发挥作用。在此,我们探讨了CCNA2在TNBC中的作用。方法:我们分析了CCNA2在15对TNBC及其邻近组织中的表达,并使用组织微阵列队列评估CCNA2表达之间的关系。此外,我们使用两个TNBC队列数据集来分析CCNA2与E2F转录因子1 (E2F1)和荧光素酶报告因子之间的相关性,以探索它们之间的关联。通过救援实验,我们分析了E2F1敲低对CCNA2表达和细胞行为的影响。结果:我们发现CCNA2在TNBC中的表达明显高于邻近组织,在MDA-MB-231和MDA-MB-468细胞中也有类似的观察结果。生物信息学分析(R= 0.80, P< 0.001)和TNBC组织验证分析(R= 0.53, P< 0.001)发现E2F1与CCNA2高度相关。我们确定E2F1结合了CCNA2启动子内的+677位点。此外,由于E2F1在TNBC中的上调,CCNA2过表达增加了细胞的增殖、侵袭和迁移。结论:我们的数据表明E2F1通过上调CCNA2的表达促进TNBC的增殖和侵袭。E2F1和CCNA2可能是有效治疗TNBC的潜在候选靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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