miR-124 interacts with the Notch1 signalling pathway and has therapeutic potential against gastric cancer

被引:42
作者
Jiang, Lei [1 ]
Lin, Tiesu [2 ]
Xu, Chaochao [2 ]
Hu, Sunkuan [2 ]
Pan, Yangyang [2 ]
Jin, Rong [2 ,3 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Cent Lab, Wenzhou, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Wenzhou, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 1, Dept Epidemiol, Wenzhou, Zhejiang, Peoples R China
关键词
miR-124; Notch1; JAG1; intracellular domain of Notch1; gastric cancer; INHIBITS CELL-PROLIFERATION; DOWN-REGULATION; BREAST-CANCER; GROWTH; METASTASIS; MICRORNAS; PROGRESSION; SUPPRESSES; INVASION; GLIOBLASTOMA;
D O I
10.1111/jcmm.12724
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aberrant Notch signalling plays an important role in cancer progression. However, little is known about the interaction between miRNA and the Notch signalling pathway and its role in gastric cancer (GC). In this study, we found that miR-124 was down-regulated in GC compared with adjacent normal tissue. Forced expression of miR-124 inhibited GC cell growth, migration and invasion, and induced cell cycle arrest. miR-124 negatively regulated Notch1 signalling by targeting JAG1. miR-124 levels were also shown to be inversely correlated with JAG1 expression in GC. Furthermore, we found that the overexpression of the intracellular domain of Notch1 repressed miR-124 expression, promoted GC cell growth, migration and invasion. Conversely, blocking Notch1 using a -secretase inhibitor up-regulated miR-124 expression, inhibited GC cell growth, migration and invasion. In conclusion, our data demonstrates a regulatory feedback loop between miR-124 and Notch1 signalling in GC cells, suggesting that the miR-124/Notch axis may be a potential therapeutic target against GC.
引用
收藏
页码:313 / 322
页数:10
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