Knockdown of SETDB1 inhibits breast cancer progression by miR-381-3p-related regulation

被引:42
作者
Wu, Milu [1 ]
Fan, Baohua [1 ]
Guo, Qijing [1 ]
Li, Yan [1 ]
Chen, Rong [1 ]
Lv, Nannan [1 ]
Diao, Yinzhuo [1 ]
Luo, Yushuang [1 ]
机构
[1] Qinghai Univ, Affiliated Hosp, Dept Oncol, 29 Tongren Rd, Xining 810001, Qinghai, Peoples R China
基金
中国国家自然科学基金;
关键词
SET domain bifurcated 1; miR-381-3p; Breast cancer; Proliferation; Cell cycle progression; Migration; HISTONE METHYLTRANSFERASE SETDB1; CELL-PROLIFERATION; MESENCHYMAL TRANSITION; STEM-CELLS; METHYLATION; METASTASIS; PATHWAY; STATISTICS; SUPPRESSES; EXPRESSION;
D O I
10.1186/s40659-018-0189-0
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: SET domain bifurcated 1 (SETDB1) has been widely considered as an oncogene playing a critical role in many human cancers, including breast cancer. Nevertheless, the molecular mechanism by which SETDB1 regulates breast cancer tumorigenesis is still unknown. Methods: qRT-PCR assay or western blot analysis was performed to assess the expression level of SETDB1 mRNA or protein, respectively. siSETDB1, pCMV6-XL5-SETDB1, miR-381-3p mimic, or miR-381-3p inhibitor was transfected into cells to regulate the expression of SETDB1 or miR-381-3p. MiRNA directly interacted with SETDB1 was verified by luciferase reporter assay and RNA immunoprecipitation. CCK-8 assay, colony formation assay, flow cytometric analysis, and transwell assay were used to detect the abilities of cell proliferation, cell cycle progression and migration, respectively. Animal model of xenograft tumor was used to observe the regulatory effect of SETDB1 on tumor growth in vivo. Results: We verified that SETDB1 mRNA level was upregulated in breast cancer tissues and cell lines, and SETDB1 depletion led to a suppression of cell proliferation, cell cycle progression and migration in vitro, as well as tumor growth in vivo. SETDB1 was verified to be a target of miR-381-3p. Moreover, miR-381-3p overexpression suppressed cell proliferation, cell cycle progression and migration, whereas SETDB1 abated miR-381-3p-mediated regulatory function on breast cancer cells. Conclusions: This study revealed that SETDB1 knockdown might suppress breast cancer progression at least partly by miR-381-3p-related regulation, providing a novel prospect in breast cancer therapy.
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页数:11
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