Abstract
BackgroundSET 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.MethodsqRT-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.ResultsWe 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.ConclusionsThis 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.
Highlights
SET domain bifurcated 1 (SETDB1) has been widely considered as an oncogene playing a critical role in many human cancers, including breast cancer
The data revealed that SETDB1 mRNA level was higher in breast cancer cell lines than that in normal MCF-10A cells (Fig. 1b)
According to the median ratio of SETDB1 mRNA expression, the 45 breast cancer patients were classified into two groups: high SETDB1 mRNA expression group (n = 24) and low SETDB1 mRNA expression group (n = 21)
Summary
SET domain bifurcated 1 (SETDB1) has been widely considered as an oncogene playing a critical role in many human cancers, including breast cancer. The molecular mechanism by which SETDB1 regulates breast cancer tumorigenesis is still unknown. SET domain bifurcated 1 (SETDB1), known as KMET1 or ESET, is a novel SET domain protein with histone H3 lysine 9 (H3K9)-specific methyltransferase activity which plays a pivotal role in early embryonic development [3]. Accumulating evidences suggest that SETDB1 might function as a novel oncogene to be involved in multiple human cancers, such as hepatocellular carcinoma [6], lung cancer [7], and sporadic cutaneous melanoma [8]. A research document demonstrated that SETDB1 was regulated by miR-7 played a critical role in the metastasis of breast cancer [9].
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