Anti-miR-203 suppresses ER-positive breast cancer growth and stemness by targeting SOCS3.
Anti-miR-203 suppresses ER-positive breast cancer growth and stemness by targeting SOCS3.
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DOI：
10.18632/oncotarget.11193
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发表时间：
2016-09-06
期刊：
影响因子：
--
通讯作者：
Ray RB
中科院分区：
文献类型：
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作者：
Muhammad N;Bhattacharya S;Steele R;Ray RB
乳腺癌是世界范围内妇女的一个主要公共卫生问题，现有的治疗方法对这种致命的疾病没有足够的效果。microRNAs（miRNAs）调控许多靶基因的表达，在包括乳腺癌在内的多种肿瘤的发生、发展和抑制中发挥着重要作用。我们先前观察到miR-203在乳腺癌组织和ER阳性乳腺癌细胞系中高度上调。在我们目前的研究中，我们观察到anti-miR-203在体外抑制乳腺癌细胞增殖。与对照MCF-7细胞相比，将miR-203耗尽的MCF-7细胞原位植入裸鼠中显示出较小的肿瘤生长。此外，与ER阴性患者相比，ER阳性乳腺癌患者中的miR-203表达显著更高。我们鉴定了细胞因子信号传导抑制因子3（SOCS3）作为miR-203的直接靶点。在此，我们观察到miR-203表达与ER阳性乳腺癌样本中SOCS3表达呈负相关。另外，我们发现anti-miR-203抑制了MCF-7和ZR-75 - 1细胞中pStat3、pERK和c-Myc的表达。我们还证明了抗miR-203减少了MCF-7和ZR-75 - 1细胞中乳腺球的形成和干细胞标志物的表达。综上所述，我们的数据表明，抗miR-203有潜力作为ER阳性乳腺癌治疗的新治疗策略。
Breast cancer is a major public health problem worldwide in women and existing treatments are not adequately effective for this deadly disease. microRNAs (miRNAs) regulate the expression of many target genes and play pivotal roles in the development, as well as in the suppression of many cancers including breast cancer. We previously observed that miR-203 was highly upregulated in breast cancer tissues and in ER-positive breast cancer cell lines. In our present study, we observed that anti-miR-203 suppresses breast cancer cell proliferation in vitro. Orthotopic implantation of miR-203 depleted MCF-7 cells into nude mice displays smaller tumor growth as compared to control MCF-7 cells. Furthermore, miR-203 expression is significantly higher in ER-positive breast cancer patients as compared to ER-negative patients. We identified suppressor of cytokine signaling 3 (SOCS3) as a direct target of miR-203. Here we observed that miR-203 expression is inversely correlated with SOCS3 expression in ER-positive breast cancer samples. Additionally, we found that anti-miR-203 suppressed the expression of pStat3, pERK and c-Myc in MCF-7 and ZR-75-1 cells. We also demonstrated that anti-miR-203 decreased mammospheres formation and expression of stem cell markers in MCF-7 and ZR-75-1 cells. Taken together, our data suggest that anti-miR-203 has potential as a novel therapeutic strategy in ER-positive breast cancer treatment.