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J Cell Mol Med. 2016 Feb;20(2):313-22. doi: 10.1111/jcmm.12724. Epub 2015 Nov 27.

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

Author information

1
Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
2
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
3
Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract

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 γ-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.

KEYWORDS:

JAG1; Notch1; gastric cancer; intracellular domain of Notch1; miR-124

PMID:
26612211
PMCID:
PMC4727557
DOI:
10.1111/jcmm.12724
[Indexed for MEDLINE]
Free PMC Article

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