The role of miR-100 in regulating apoptosis of breast cancer cells.

The role of miR-100 in regulating apoptosis of breast cancer cells.
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DOI:
10.1038/srep11650
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发表时间:
2015-07-01
期刊:
影响因子:
4.6
通讯作者:
Zhang X
Zhang X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gong Y;He T;Yang L;Yang G;Chen Y;Zhang X

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乳腺癌是一个严重的全球性健康问题。细胞凋亡的抑制在乳腺癌的发生中起着重要的作用。microRNAs(miRNAs)在细胞凋亡的调控中起着重要的作用。然而,miRNAs对乳腺癌细胞凋亡的调控作用尚未得到深入研究。为了解决这个问题,在本研究中,miR-100对不同乳腺癌细胞的细胞增殖的影响被表征。结果显示,与其他人乳腺癌细胞(MCF 7、MDA-MB-453、T47 D、HCC 1954和SUM 149)相比,miR-100在SK-BR-3细胞中显著上调。用抗miRNA-100寡核苷酸(AMO-miR-100)沉默miR-100表达在体外和体内引发SK-BR-3细胞凋亡。然而,miR-100的过表达导致miR-100下调的乳腺癌细胞的增殖抑制。miR-100在SK-BR-3细胞中的拮抗作用增加了miR-100的靶基因MTMR 3的表达,从而导致p27的激活,并最终导致G2/M细胞周期停滞和凋亡。miR-100的下调使SK-BR-3细胞对化疗敏感。因此,我们的发现突出了miR-100-MTMR 3-p27通路在乳腺癌分子病因学中的新方面。
Breast cancer is a serious health problem worldwide. Inhibition of apoptosis plays a major role in breast cancer tumorigenesis. MicroRNAs (miRNAs) play crucial roles in the regulation of apoptosis. However, the regulation of breast cancer apoptosis by miRNAs has not been intensively investigated. To address this issue, the effect of miR-100 on the cell proliferation of different breast cancer cells was characterized in the present study. The results showed that miR-100 was significantly upregulated in SK-BR-3 cells compared with other human breast cancer cells (MCF7, MDA-MB-453, T47D, HCC1954 and SUM149). Silencing miR-100 expression with anti-miRNA-100 oligonucleotide (AMO-miR-100) initiated apoptosis of SK-BR-3 cells in vitro and in vivo. However, the overexpression of miR-100 led to the proliferation inhibition of the miR-100-downregulated breast cancer cells. Antagonism of miR-100 in SK-BR-3 cells increased the expression of MTMR3, a target gene of miR-100, which resulted in the activation of p27 and eventually led to G2/M cell-cycle arrest and apoptosis. The downregulation of miR-100 sensitized SK-BR-3 cells to chemotherapy. Therefore, our finding highlights a novel aspect of the miR-100-MTMR3-p27 pathway in the molecular etiology of breast cancer.
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