背景:三阴性乳腺癌(TNBC)是乳腺癌的分子亚型,这是全世界女性的主要健康负担。百里酚(TQ),一种天然化合物,已经发现对TNBC细胞有效,本研究确定IL17RD是TQ在TNBC细胞中的新靶标。
方法:我们通过MBD1(甲基-CpG结合域蛋白1)抗体进行了染色质免疫沉淀序列(ChIP-Seq),以鉴定受TQ影响的全基因组甲基化位点。ChIP-seq鉴定出136个基因,包括肿瘤抑制因子IL17RD,作为TQ的新目标,TQ在TNBC细胞系BT-549和MDA-MB-231中进行表观遗传学上调。通过Kaplan-Meier分析研究IL17RD表达和生存结果。
结果:TQ处理抑制了生长,迁移,和有或没有IL17RD过表达或敲低的TNBC细胞的侵袭,而IL17RD过表达和TQ处理的组合对TNBC细胞最有效。此外,IL17RD的高表达与TNBC患者的生存期更长有关,表明TQ和IL17RD对TNBC的潜在治疗作用。
结论:我们的数据表明,TQ可能在TNBC细胞系中表观遗传学上调IL17RD,这可能是TQ对TNBC细胞发挥抗癌和抗转移作用的机制之一。
BACKGROUND: Triple negative breast cancer (TNBC) is a molecular subtype of breast cancer, which is a major health burden of females worldwide. Thymoquinone (TQ), a natural compound, has been found to be effective against TNBC cells, and this study identified
IL17RD as a novel target of TQ in TNBC cells.
METHODS: We have performed chromatin immunoprecipitation Sequence (ChIP-Seq) by MBD1 (methyl-CpG binding domain protein 1) antibody to identify genome-wide methylated sites affected by TQ. ChIP-seq identified 136 genes, including the tumor suppressor
IL17RD, as a novel target of TQ, which is epigenetically upregulated by TQ in TNBC cell lines BT-549 and MDA-MB-231. The
IL17RD expression and survival outcomes were studied by Kaplan-Meier analysis.
RESULTS: TQ treatment inhibited the growth, migration, and invasion of TNBC cells with or without IL17RD overexpression or knockdown, while the combination of IL17RD overexpression and TQ treatment were the most effective against TNBC cells. Moreover, higher expression of
IL17RD is associated with longer survival in TNBC patients, indicating potential therapeutic roles of TQ and
IL17RD against TNBC.
CONCLUSIONS: Our data suggest that IL17RD might be epigenetically upregulated in TNBC cell lines by TQ, and this might be one of the mechanisms by which TQ exerts its anticancer and antimetastatic effects on TNBC cells.