Department of Pathology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, P.R. China.
Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.
Oncol Rep. 2019 Feb;41(2):1284-1292. doi: 10.3892/or.2018.6871. Epub 2018 Nov 19.
SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 methyltransferase that is highly expressed in various tumor types, including breast cancer. However, how SETDB1 functions in breast cancer is unclear. In the present study, proliferation, migration and invasion assays were performed to explore the role of SETDB1 in breast cancer cells. SETDB1 downregulation in BT549 and MDA‑MB‑231 cells reduced cell proliferation, whereas upregulation in MCF7 and T47D cells enhanced proliferation. Depletion of SETDB1 suppressed cell migration and invasion in vitro and reduced lung metastasis in vivo. By contrast, SETDB1 overexpression enhanced cell migration and invasiveness. Notably, SETDB1 overexpression appeared to induce epithelial‑mesenchymal transition (EMT) in MCF7 cells. Mechanistic investigations indicated that SETDB1 acts as an EMT inducer by binding directly to the promoter of the transcription factor Snail. Thus, SETDB1 is involved in breast cancer metastasis and may be a therapeutic target for treating patients with breast cancer.
SET 结构域分隔蛋白 1（SETDB1）是一种组蛋白 H3 赖氨酸 9 甲基转移酶，在包括乳腺癌在内的多种肿瘤类型中高度表达。然而，SETDB1 在乳腺癌中的作用尚不清楚。在本研究中，通过增殖、迁移和侵袭实验探讨了 SETDB1 在乳腺癌细胞中的作用。BT549 和 MDA-MB-231 细胞中 SETDB1 的下调降低了细胞增殖，而 MCF7 和 T47D 细胞中 SETDB1 的上调增强了增殖。SETDB1 的耗竭抑制了细胞的迁移和侵袭，并减少了体内的肺转移。相比之下，SETDB1 的过表达增强了细胞的迁移和侵袭能力。值得注意的是，SETDB1 的过表达似乎诱导了 MCF7 细胞中的上皮-间充质转化（EMT）。机制研究表明，SETDB1 通过直接结合转录因子 Snail 的启动子，作为 EMT 诱导剂发挥作用。因此，SETDB1 参与了乳腺癌转移，可能是治疗乳腺癌患者的治疗靶点。
