我国科学家发现引发胃癌的特殊microRNA分子—miR-7

  近日，来自中国第四军医大学的研究人员通过研究发现，microRNA 分子miR-7可以通过抑制一种关键的信号通路来抑制胃癌的发生，而这种关键的信号通路对于幽门螺杆菌而言是一种保护性的机制，该研究或为后期讯号诱导子miR-7表达进而来有效抑制胃癌的新型药物或疗法的开发提供新的线索和研究思路。
  据国立卫生研究院数据显示，胃癌是常见的四种癌症中的一种，而且其是全世界癌症死亡的第三大主要原因；在胃癌中表达水平较低的miR-7可以通过抑制特殊的生长因子受体（IGF1R）来阻断癌细胞向其它组织的扩散；然而miR-7是否可以抑制胃癌的早期发生目前研究者尚不清楚。
  文章中研究者对miR-7的新型作用靶点进行了筛选，研究者Dai-Ming Fan院士表示，miR-7可以直接作用基因RELA和FOS，这两个基因可以编码参与致癌NF-κB和AP-1信号通路的蛋白的产生；在人类的胃癌样本中，低水平的miR-7往往和RELA和FOS的高水平表达及患者低生存率直接相关；然而增加miR-7的水平可以降低RELA和FOS的水平并且抑制小鼠机体肿瘤的生长。
  随后研究者发现，为了直接抑制RELA的表达，miR-7会通过靶向作用NF-κB途径上的上游激酶IKKε来控制蛋白的激活，然而同样的途径本身就可以抑制miR-7的表达，这就表明，如果NF-κB途径被强烈激活的话，miR-7或许就不能RELA的活性了。
  慢性的幽门螺杆菌感染是引发胃癌的主要风险因素，部分原因可能是因为幽门螺杆菌会高度激活NF-κB的途径，而本文研究中Fan和其同事发现，在胃部组织细胞中培养幽门螺杆菌会激活IKKε和NF-κB，同时会降低miR-7的表达，而这对于促进正常的胃部细胞变成癌细胞或是一种潜在的关键步骤。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

MicroRNA-7/NF-κB signaling regulatory feedback circuit regulates gastric carcinogenesis
Journal of Cell Biology   doi: 10.1083/jcb.201501073
Xiao-Di Zhao,1,* Yuan-Yuan Lu,1,* Hao Guo,1,* Hua-Hong Xie,1 Li-Jie He,1,2 Gao-Fei Shen,1 Jin-Feng Zhou,1 Ting Li,1 Si-Jun Hu,1 Lin Zhou,1 Ya-Nan Han,1 Shu-Li Liang,1 Xin Wang,1 Kai-Chun Wu,1 Yong-Quan Shi,1 Yong-Zhan Nie,1 and Dai-Ming Fan1
MicroRNAs play essential roles in gene expression regulation during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer (GC). We used genome-wide screenings and identified RELA and FOS as novel targets of miR-7. Overexpression of miR-7 repressed RELA and FOS expression and prevented GC cell proliferation and tumorigenesis. These effects were clinically relevant, as low miR-7 expression was correlated with high RELA and FOS expression and poor survival in GC patients. Intriguingly, we found that miR-7 indirectly regulated RELA activation by targeting the IκB kinase IKKε. Furthermore, IKKε and RELA can repress miR-7 transcription, which forms a feedback circuit between miR-7 and nuclear factor κB (NF-κB) signaling. Additionally, we demonstrate that down-regulation of miR-7 may occur as a result of the aberrant activation of NF-κB signaling by Helicobacter pylori infection. These findings suggest that miR-7 may serve as an important regulator in GC development and progression.