Up-regulation of matrix metalloproteinases in a mouse model of chemically induced colitis-associated cancer: the role of microRNAs.
Up-regulation of matrix metalloproteinases in a mouse model of chemically induced colitis-associated cancer: the role of microRNAs.
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化学诱导结肠炎相关癌症小鼠模型中基质金属蛋白酶的上调：microRNA 的作用
DOI：
10.18632/oncotarget.3027
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Shen S
中科院分区：
文献类型：
--
作者：
Ai F;Zhang X;Li X;Qin Z;Ye Q;Tian L;Tang A;Li N;Li G;Ma J;Shen S
新出现的证据表明microRNA参与调节多种炎症介质的产生，包括细胞因子和趋化因子。我们先前阐明了将结肠炎与结直肠癌联系起来的关键信号的动态激活。在这项研究中，我们观察到基质金属蛋白酶（Mmps）水平的急剧增加，这为炎症-癌症联系提供了基础，我们质疑这是否是Mmp特异性microRNA失调的结果，至少部分如此。我们分析了一组预测靶向Mmps的小鼠microRNA，发现它们在炎症-癌症联系中下调。此外，我们证明了三种小鼠microRNA，即miR-128，-134和-330，可以分别靶向三种Mmp Mmp 3，Mmp 10和Mmp 13。我们还发现，microRNA加工酶Dicer 1的水平在炎症-癌症联系中降低。这些microRNA在结肠癌细胞中起肿瘤抑制剂的作用，减弱鼠结肠癌细胞的增殖、迁移和侵袭潜力，以及血管生成和源自这些细胞的肿瘤的生长。我们的研究结果表明，microRNA调节关键炎症介质的产生，microRNA功能障碍可能导致与癌症相关的非消退性炎症。
Emerging evidence has implicated microRNAs in regulating the production of multiple inflammatory mediators including cytokines and chemokines. We previously elucidated the dynamic activation of key signals that link colitis to colorectal cancer. In this study, we observed a sharp increase in the levels of matrix metalloproteinases (Mmps) that provided a basis for the inflammation-cancer link, and we questioned whether this was a consequence of the dysregulation of Mmp-specific microRNAs, at least partly. We assayed a panel of murine microRNAs that were predicted to target Mmps and found they were downregulated in the inflammation-cancer link. Furthermore, we demonstrated that three murine microRNAs, namely miR-128, -134, and -330, can target the three Mmps Mmp3, Mmp10, and Mmp13, respectively. We also found that the level of the microRNA-processing enzyme Dicer1 was decreased in the inflammation-cancer link. These microRNAs functioned as tumor suppressors in colon cancer cells, attenuating the proliferation, migration, and invasion potential of murine colon cancer cells as well as angiogenesis and the growth of tumors derived from these cells. Our results suggest that microRNAs modulate the production of key inflammatory mediators and that microRNA dysfunction may contribute to the non-resolving inflammation associated with cancer.
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影响因子：
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作者：
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