期刊
MOLECULAR THERAPY
卷 27, 期 6, 页码 1166-1182出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2019.02.002
关键词
-
资金
- National Natural Science Foundation of China [81472314, 81602705, 81772580]
Transforming growth factor beta (TGF-beta) drives epithelial-mesenchymal transition (EMT), playing vital roles in cancer metastasis. The crosstalk between microRNAs (miRNAs) and TGF-beta are frequently observed and involved in TGF-beta-induced EMT. Here, we determine that miR-577 is significantly upregulated in gastric cancer (GC). miR-577 expression is positively correlated with GC metastasis status and poor patient prognosis. Functional assays demonstrate that miR-577 promotes metastasis and chemoresistance by inducing EMT and stemness-like properties. Moreover, TGF-beta promotes the expression of miR-577, and miR-577 participates TGF-beta-mediated cancer metastasis. Mechanistically, TGF-b activates miR-577 via NF-kappa B-mediated transcription, and miR-577 enhances TGF-beta signaling by targeting the serum deprivation protein response (SDPR), which directly interacts with ERK to inactivate the ERK-NF-kappa B pathway, hence forming a feedback loop to drive tumor metastasis. A plausible mechanism of EMT induction by the TGF-beta network is elucidated. Our findings suggest that the TGF-beta-miR-577-SDPR axis may be a potential prognostic marker and therapeutic target against cancer metastasis in GC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据