Ma Xiaodong, Yan Fang, Deng Qipan, Li Fenge, Lu Zhongxin, Liu Mofang, Wang Lisheng, Conklin Daniel J, McCracken James, Srivastava Sanjay, Bhatnagar Aruni, Li Yong
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY, USA; Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, KY, USA; Institute of Pharmaceutical Research, South China Normal University, Guangzhou, China.
Department of Histology and Embryology; Southern Medical University , Guangzhou, China.
Cell Discov. 2015 May 19;1:15005. doi: 10.1038/celldisc.2015.5. eCollection 2015.
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.
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。微小RNA-301a（miR-301a）是核因子κB（NF-κB）和信号转导与转录激活因子3（Stat3）的激活剂，在这两种致命恶性肿瘤中均过表达。在这项研究中，我们表明miR-301a的基因敲除可减少Kras驱动的小鼠肺癌发生。并且miR-301a缺乏可保护动物免受葡聚糖硫酸钠诱导的结肠炎症和结肠炎相关的结肠癌发生。我们还证明，骨髓来源细胞中miR-301a的缺失可减弱结肠癌发生模型中的肿瘤生长。我们的研究结果确定，一种微小RNA——miR-301a——在体内激活两条主要的炎症途径（NF-κB和Stat3），产生促进肿瘤发生的促炎微环境。
Zotero 插件
