miR-200c inhibits breast cancer proliferation by targeting KRAS.
miR-200c inhibits breast cancer proliferation by targeting KRAS.
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miR-200c 通过靶向 KRAS 抑制乳腺癌增殖
DOI：
10.18632/oncotarget.5198
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发表时间：
2015-10-27
期刊：
影响因子：
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通讯作者：
Xie X
中科院分区：
文献类型：
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作者：
Song C;Liu LZ;Pei XQ;Liu X;Yang L;Ye F;Xie X;Chen J;Tang H;Xie X
microRNA，miR-200 c，参与多种癌症的肿瘤发生和进展。本研究旨在探讨miR-200 c在乳腺癌中的表达、作用机制及预后作用。我们发现miR-200 c在乳腺癌组织和细胞系中均下调，使用定量实时PCR（qRT-PCR）。原位杂交（ISH）和微阵列显示，低miR-200 c表达与患者总生存期（OS）和无病生存期（DFS）相关。我们使用荧光素酶报告质粒发现miR-200 c通过直接靶向KRAS抑制AKT和ERK通路。miR-200 c对KRAS的抑制在体外和体内抑制了乳腺癌细胞的增殖和存活。miR-200 c还通过在异种移植小鼠模型中负调节KRAS而具有抗肿瘤作用。我们的研究结果提供了关于miR-200 c在乳腺癌中作为肿瘤抑制因子的作用的线索，其通过在体外和体内抑制KRAS翻译来实现。miR-200 c可能成为乳腺癌潜在的治疗靶点。
The microRNA, miR-200c, is involved in the tumorigenesis and progression of a variety of cancers. The purpose of this study was to investigate the expression, mechanism and prognostic roles of miR-200c in breast cancer. We found that miR-200c was downregulated in both breast cancer tissue and cell lines using quantitative real-time PCR (qRT-PCR). In situ hybridization (ISH) and microarrays showed that low miR-200c expression was associated with poor patient overall survival (OS) and disease free survival (DFS). We used luciferase reporter plasmids to find that miR-200c inhibited the AKT and ERK pathways by directly targeting KRAS. Repression of KRAS by miR-200c suppressed the proliferation and survival of breast cancer cells in vitro and in vivo. miR-200c also had an anti-tumor effect by negatively regulating KRAS in a xenograft mouse model. Our findings provide clues regarding the role of miR-200c as a tumor suppressor in breast cancer through the inhibition of KRAS translation both in vitro and in vivo. miR-200c could be a potential therapeutic target in breast cancer.