姜黄素通过上调 IL17RD 控制三阴性乳腺癌细胞的体外生长和转移。
Thymoquinone upregulates IL17RD in controlling the growth and metastasis of triple negative breast cancer cells in vitro.
机构信息
Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China.
Division of Molecular Cancer Biology, The Red-Green Research Center, Dhaka, 1205, Bangladesh.
出版信息
BMC Cancer. 2022 Jun 27;22(1):707. doi: 10.1186/s12885-022-09782-z.
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.
背景
三阴性乳腺癌（TNBC）是乳腺癌的一种分子亚型，是全球女性的主要健康负担。胸腺醌（TQ），一种天然化合物，已被发现对 TNBC 细胞有效，本研究确定 IL17RD 是 TQ 在 TNBC 细胞中的一个新靶点。
方法
我们通过 MBD1（甲基-CpG 结合域蛋白 1）抗体进行染色质免疫沉淀测序（ChIP-Seq），以确定受 TQ 影响的全基因组甲基化位点。ChIP-seq 确定了 136 个基因，包括肿瘤抑制因子 IL17RD，是 TQ 的一个新靶点，TQ 在 TNBC 细胞系 BT-549 和 MDA-MB-231 中通过表观遗传上调 IL17RD 的表达。通过 Kaplan-Meier 分析研究了 IL17RD 的表达和生存结果。
结果
TQ 治疗抑制了 TNBC 细胞的生长、迁移和侵袭，无论是否过表达或敲低 IL17RD，而 IL17RD 过表达和 TQ 治疗的组合对 TNBC 细胞最有效。此外，IL17RD 的高表达与 TNBC 患者的生存时间延长相关，表明 TQ 和 IL17RD 对 TNBC 具有潜在的治疗作用。
结论
我们的数据表明，TQ 可能通过表观遗传上调 TNBC 细胞系中的 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。
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