title: miR-124 interacts with the Notch1 signalling pathway and has therapeutic potential against gastric cancer.
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.
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Tiesu
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Chaochao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Sunkuan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.|Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D053829:Amyloid Precursor Protein Secretases
keywords: JAG1; Notch1; gastric cancer; intracellular domain of Notch1; miR-124