The Curcumin Analog EF24 Inhibits Proliferation and Invasion of Triple-Negative Breast Cancer Cells by Targeting the Long Noncoding RNA HCG11/Sp1 Axis
The Curcumin Analog EF24 Inhibits Proliferation and Invasion of Triple-Negative Breast Cancer Cells by Targeting the Long Noncoding RNA HCG11/Sp1 Axis
复制标题
姜黄素类似物 EF24 通过靶向长非编码 RNA HCG11/Sp1 轴抑制三阴性乳腺癌细胞的增殖和侵袭
DOI：
10.1128/mcb.00163-21
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发表时间：
2022-01-01
影响因子：
5.3
通讯作者：
Lv, Xiao-Ai
中科院分区：
文献类型：
--
作者：
Duan, Yin;Chen, Hui-Ling;Lv, Xiao-Ai
EF24是一种姜黄素类似物，对多种癌症具有有效的抗肿瘤作用。然而，EF24是否延缓三阴性乳腺癌（TNBC）的进展仍不清楚。在本研究中，我们探讨了EF24在TNBC中的作用，并阐明了潜在的机制。在TNBC异种移植物的小鼠模型中，EF24给药减小了肿瘤体积，抑制了细胞增殖，促进了细胞凋亡，并下调了长非编码RNA人白细胞抗原复合物11（HCG 11）的表达。在TNBC细胞系中，EF24给药降低了细胞活力，抑制了细胞侵袭，并下调了HCG 11表达。HCG 11过表达可重新增强EF24抑制的TNBC细胞系的增殖和侵袭。以下机制研究揭示，HCG 11过表达通过减少其泛素化而提高Sp1转录因子（Sp1）的表达，从而增强Sp1介导的TNBC细胞系中的细胞存活和侵袭。最后，体内研究表明，HCG 11过表达的TNBC异种移植物对EF 24治疗的反应性较低。总之，EF24处理降低了HCG 11的表达，导致Sp1表达的降解，从而抑制了TNBC细胞的增殖和侵袭。
EF24, a curcumin analog, exerts a potent antitumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long noncoding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression reenhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.