Modulation of tumorigenesis by the pro-inflammatory microRNA miR-301a in mouse models of lung cancer and colorectal cancer.
Modulation of tumorigenesis by the pro-inflammatory microRNA miR-301a in mouse models of lung cancer and colorectal cancer.
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促炎性 microRNA miR-301a 在肺癌和结直肠癌小鼠模型中调节肿瘤发生
DOI：
10.1038/celldisc.2015.5
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发表时间：
2015
期刊：
影响因子：
33.5
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Ma X;Yan F;Deng Q;Li F;Lu Z;Liu M;Wang L;Conklin DJ;McCracken J;Srivastava S;Bhatnagar A;Li Y
肺癌和结直肠癌占美国所有癌症死亡人数的三分之一以上。MicroRNA-301a(miR-301a)是核因子-κB(NF-κB)和STAT3的激活剂，在这两种致命性恶性肿瘤中均有过表达。在这项工作中，我们证明了miR-301a的遗传消融减少了Kras驱动的小鼠肺肿瘤的发生。MiR-301a缺乏保护动物免受葡聚糖硫酸钠诱导的结肠炎和结肠炎相关结肠癌的发生。我们还证明，在结肠癌发生模型中，骨髓来源细胞中miR-301a的缺失可以抑制肿瘤的生长。我们的发现确定，一个微小RNA-miR-301a-在体内激活两个主要的炎症途径(NF-κB和STAT3)，产生促进肿瘤发生的促炎微环境。
Lung cancer and colorectal cancer account for over one-third of all cancer deaths in the United States. MicroRNA-301a (miR-301a) is an activator of both nuclear factor-κB (NF-κB) and Stat3, and is overexpressed in both deadly malignancies. In this work, we show that genetic ablation of miR-301a reduces Kras-driven lung tumorigenesis in mice. And miR-301a deficiency protects animals from dextran sodium sulfate-induced colon inflammation and colitis-associated colon carcinogenesis. We also demonstrate that miR-301a deletion in bone marrow-derived cells attenuates tumor growth in the colon carcinogenesis model. Our findings ascertain that one microRNA—miR-301a—activates two major inflammatory pathways (NF-κB and Stat3) in vivo, generating a pro-inflammatory microenvironment that facilitates tumorigenesis.