Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.
Mol Cell Biol. 2022 Jan 20;42(1):e0016321. doi: 10.1128/MCB.00163-21. Epub 2021 Nov 15.
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 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.
EF24 是一种姜黄素类似物,对多种癌症具有强大的抗肿瘤作用。然而,EF24 是否能延缓三阴性乳腺癌(TNBC)的进展尚不清楚。在本研究中,我们探讨了 EF24 在 TNBC 中的作用,并阐明了其潜在的机制。在 TNBC 异种移植小鼠模型中,EF24 给药可降低肿瘤体积、抑制细胞增殖、促进细胞凋亡,并下调长链非编码 RNA 人类白细胞抗原复合体 11(HCG11)的表达。在 TNBC 细胞系中,EF24 给药降低细胞活力、抑制细胞侵袭,并下调 HCG11 的表达。HCG11 的过表达可逆转 EF24 抑制的 TNBC 细胞系的增殖和侵袭。以下的机制研究表明,HCG11 的过表达通过减少其泛素化来提高 Sp1 转录因子(Sp1)的表达,从而增强 Sp1 介导的 TNBC 细胞的存活和侵袭。最后,该研究表明,HCG11 过表达的 TNBC 异种移植瘤对 EF24 治疗的反应性较低。总之,EF24 治疗可降低 HCG11 的表达,导致 Sp1 表达的降解,从而抑制 TNBC 细胞的增殖和侵袭。