The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer.
The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer.
复制标题
DOI：
10.3390/ijms17081298
复制
发表时间：
2016-08-10
影响因子：
5.6
通讯作者：
Eroles P
中科院分区：
文献类型：
--
作者：
Cabello P;Pineda B;Tormo E;Lluch A;Eroles P
二甲双胍是一种被批准用于治疗II型糖尿病的药物，它与减少乳腺癌和转移的发生率以及提高糖尿病乳腺癌患者的存活率有关。MiR-26a的高水平表达被认为是这种作用的可能机制之一；同样，这种miRNA也与乳腺癌的生存/凋亡过程有关。我们的目的是评估miR-26a及其部分靶点是否能够介导二甲双胍在乳腺癌中的作用。用四甲基偶氮唑盐比色法检测异位过表达和/或下调miR-26a对乳腺癌细胞株MDA-MB-231、MDA-MB-468和MCF-7的生长抑制作用。同样，用定量聚合酶链式反应(PCR)检测靶基因CASP3、CCNE2、ABL2、APAF1、XIAP、BCL-2、PTEN、P53、E2F3、CDC25A、BCL2L1、MCL-1、EZH2和MTDH的表达水平。观察二甲双胍对乳腺癌细胞活力的影响以及对miR-26a、bcl2、PTEN、mcl1、EZH2和MTDH的调节作用。创面愈合实验分析miR-26a和二甲双胍对细胞迁移的影响。MIR-26a过表达导致细胞活力下降，通过抑制细胞活力可部分恢复细胞活力。MiR-26a可下调E2F3、MCL-1、EZH2、MTDH和PTEN的表达，同时下调PTEN(磷酸酶和张力蛋白同源)蛋白的表达。二甲双胍治疗降低了乳腺癌细胞的活力，增加了miR-26a的表达，并导致bcl2、EZH2和PTEN的表达减少。抑制MIR-26a可部分阻断二甲双胍的活性效应以及PTEN和EZH2的表达下调。我们的结果表明，二甲双胍有效地降低了乳腺癌细胞的活力，提示该药物的作用是通过增加miR-26a的表达及其靶点PTEN和EHZ2的减少来实现的。因此，二甲双胍用于乳腺癌的治疗是一种有前景的乳腺癌治疗方法。
Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer. The viability of MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cell lines was evaluated with an MTT assay after ectopic overexpression and/or downregulation of miR-26a. Similarly, the expression levels of the miR-26a targets CASP3, CCNE2, ABL2, APAF1, XIAP, BCL-2, PTEN, p53, E2F3, CDC25A, BCL2L1, MCL-1, EZH2, and MTDH were assessed by quantitative polymerase chain reaction (PCR). The effect of metformin treatment on breast cancer cell viability and miR-26a, BCL-2, PTEN, MCL-1, EZH2, and MTDH modulation were evaluated. Wound healing experiments were performed to analyze the effect of miR-26a and metformin treatment on cell migration. MiR-26a overexpression resulted in a reduction in cell viability that was partially recovered by inhibiting it. E2F3, MCL-1, EZH2, MTDH, and PTEN were downregulated by miR-26a and the PTEN (phosphatase and tensin homolog) protein was also reduced after miR-26a overexpression. Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression. miR-26a inhibition partly prevents the metformin viability effect and the PTEN and EZH2 expression reduction. Our results indicate that metformin effectively reduces breast cancer cell viability and suggests that the effects of the drug are mediated by an increase in miR-26a expression and a reduction of its targets, PTEN and EHZ2 Thus, the use of metformin in breast cancer treatment constitutes a promising potential breast cancer therapy.
登录
查看更多内容
MiR-26a 通过抑制 MCL-1 抑制乳腺癌的增殖和迁移。
影响因子：
3.7
作者：
Gao J;Li L;Wu M;Liu M;Xie X;Guo J;Tang H;Xie X
通讯作者：
Xie X
影响因子：
3.9
作者：
Anisimov, VN;Berstein, LM;Franceschi, C
通讯作者：
Franceschi, C
影响因子：
14.9
作者：
Huang DW;Sherman BT;Tan Q;Kir J;Liu D;Bryant D;Guo Y;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
DOI：
10.1158/1940-6207.capr-11-0299
发表时间：
2012-03
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Bao B;Wang Z;Ali S;Ahmad A;Azmi AS;Sarkar SH;Banerjee S;Kong D;Li Y;Thakur S;Sarkar FH
通讯作者：
Sarkar FH
影响因子：
10.5
作者：
Huse, Jason T.;Brennan, Cameron;Holland, Eric C.
通讯作者：
Holland, Eric C.