MiR-33a functions as a tumor suppressor in triple-negative breast cancer by targeting EZH2
MiR-33a functions as a tumor suppressor in triple-negative breast cancer by targeting EZH2
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DOI：
10.1186/s12935-020-1160-z
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发表时间：
2020-03-18
影响因子：
5.8
通讯作者：
Li, Weizhan
中科院分区：
文献类型：
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作者：
Zeng, Weihua;Zou, Guorong;Li, Weizhan
越来越多的研究证实microRNA在乳腺癌的进展中起重要作用，尤其是在三阴性乳腺癌（triple-negative breast cancer，TNBC）中。本研究的目的是研究miR-33 a在TNBC进展中的作用。方法采用PCR方法检测miR-33 a和EZH 2在TNBC组织、癌旁组织和细胞系中的表达。采用Western blot、CCK 8、Transwell、细胞集落形成和EdU细胞增殖、细胞周期分析和荧光素酶报告基因分析来确定miR-33 a/EZH 2在TNBC进展中的调控。结果miR-33 a在TNBC组织和细胞系中表达明显下调。miR-33 a在TNBC细胞中的过表达显著抑制细胞生长和运动，并诱导G1细胞周期停滞。荧光素酶报告基因测定显示EZH 2是miR-33 a的直接靶标，并且它在TNBC组织和细胞系中上调。miR-33 a与EZH 2在TNBC组织中的表达呈负相关。EZH 2基因敲减对TNBC细胞的恶性行为具有相似的抑制作用，而EZH 2基因的异位表达对miR-33 a过表达诱导的TNBC细胞恶性行为具有抑制作用。结论miR-33 a是一种具有抑瘤作用的miRNA，可直接作用于EZH 2，抑制TNBC细胞的增殖和迁移，诱导G1期阻滞。
Background Increasing 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. Methods PCR 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. Results MiR-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. Conclusions These 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.