MicroRNA-7/NF-κB signaling regulatory feedback circuit regulates gastric carcinogenesis.
MicroRNA-7/NF-κB signaling regulatory feedback circuit regulates gastric carcinogenesis.
复制标题
MicroRNA-7/NF-kappa B信号调节反馈回路调控胃癌发生
DOI：
10.1083/jcb.201501073
复制
发表时间：
2015-08-17
期刊：
影响因子：
--
通讯作者：
Fan DM
中科院分区：
文献类型：
--
作者：
Zhao XD;Lu YY;Guo H;Xie HH;He LJ;Shen GF;Zhou JF;Li T;Hu SJ;Zhou L;Han YN;Liang SL;Wang X;Wu KC;Shi YQ;Nie YZ;Fan DM
MERA和FOS是胃癌细胞miR-7的靶点，miR-7/IKKε/RelA相互反馈环在幽门螺杆菌感染诱发胃癌中起重要作用。在癌变过程中，microRNAs在基因表达调控中发挥着重要作用。在这里，我们研究了miR-7在胃癌(GC)中的作用及其调控机制。我们使用全基因组筛选，并将relA和fos确定为miR-7的新靶点。MiR-7过表达抑制了relA和fos的表达，阻止了GC细胞的增殖和肿瘤的发生。这些效应在临床上是相关的，因为miR-7低表达与高RelA和FOS表达以及GC患者的低生存率相关。有趣的是，我们发现miR-7通过靶向IκB激酶ikkε间接调节RelA的激活。此外，IKKε和RELA可以抑制miR-7的转录，从而在miR-7和核因子κB(NF-κB)信号之间形成反馈电路。此外，我们还证明，幽门螺杆菌感染导致的NF-κB信号的异常激活可能导致miR-7的下调。这些发现提示miR-7可能在GC的发生发展过程中起着重要的调节作用。
RELA and FOS are targets of miR-7 in gastric cancer cells and the miR-7/IKKε/RELA reciprocal feedback loop is important for gastric cancer induced by H. pylori infection. 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.