Abstract
BackgroundIncreasing reports have confirmed that microRNAs play an important role in breast cancer progression, particularly in triple-negative breast cancer (TNBC). The aim of our study was to investigate the role of miR-33a in TNBC progression.MethodsPCR assays were performed to detect miR-33a and EZH2 expression in TNBC tissues, adjacent nontumor tissues and cell lines. Western blot, CCK8, Transwell, cell colony formation and EdU cell proliferation, cell cycle analysis and luciferase reporter assays were used to determine the regulation of miR-33a/EZH2 in TNBC progression.ResultsMiR-33a was significantly downregulated in TNBC tissues and cell lines. MiR-33a overexpression in TNBC cells significantly inhibited cell growth and mobility and induced G1 cell cycle arrest. The luciferase reporter assay revealed that EZH2 is a direct target of miR-33a and that it was upregulated in TNBC tissues and cell lines. There was a negative correlation between miR-33a and EZH2 expression in TNBC tissues. EZH2 knockdown exerted similar inhibitory effects, while ectopic expression of EZH2 showed suppressive effects on malignant behaviors induced by miR-33a overexpression in TNBC cells.ConclusionsThese findings revealed that miR-33a is a tumor-suppressive miRNA in TNBC and can inhibit proliferation and mobility and induce G1 cell cycle arrest by directly targeting EZH2.
Highlights
Increasing reports have confirmed that microRNAs play an important role in breast cancer progression, in triple-negative breast cancer (TNBC)
We found that a complementary miR33a sequence was present in the 3′-Untranslated regions (3′-UTR) of enhancer of zeste homolog 2 (EZH2) mRNA (Fig. 3b), EZH2 was selected for further investigations
The number of migrated and invasive cells, and the expression levels of MMP9 mRNA and protein were significantly decreased in cells transfected with miR-33a mimics, which can be reversed by ectopic expression of EZH2 (Fig. 6j–l, and Additional file 3: Figure S3B). These results demonstrate that EZH2 overexpression antagonizes miR-33a-mediated inhibitory effect on TNBC cell behaviors, which implies that EZH2 is a downstream target of miR-33a
Summary
Increasing reports have confirmed that microRNAs play an important role in breast cancer progression, in triple-negative breast cancer (TNBC). MicroRNAs (miRNAs) are a class of highly conserved small noncoding single-stranded RNA molecules [10]. They can regulate a variety of cellular processes, including cell proliferation, mobility, differentiation and metabolism, by base-pairing with the 3′-untranslated regions (3′-UTRs) of target genes [11]. MiR-33a was upregulated after treatment with chidamide in TNBC and suppressed glycolysis by targeting LDHA [19]. It can target ADAM9 and ROS1 to suppress BC proliferation and metastasis [18]. The detailed mechanisms of miR-33a in TNBC proliferation and mobility remain unclear
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