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Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
miR-124 interacts with the Notch1 signalling pathway and has therapeutic potential against gastric cancer
Lei Jiang1, Tiesu Lin2, Chaochao Xu2
1Central Laboratory, 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.
Insights
MicroRNA-124 (miR-124) is down-regulated in gastric cancer (GC) and inhibits its growth. This study reveals a feedback loop between miR-124 and Notch1 signalling, offering a potential therapeutic target for GC.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Aberrant Notch signalling is implicated in cancer progression.
- The interplay between microRNAs (miRNAs) and the Notch pathway in gastric cancer (GC) remains largely unexplored.
Purpose of the Study:
- To investigate the role of miR-124 in gastric cancer.
- To elucidate the relationship between miR-124 and Notch signalling in GC.
- To identify potential therapeutic targets for GC treatment.
Main Methods:
- Quantitative real-time PCR to assess miR-124 expression in GC tissues.
- Cell proliferation, migration, and invasion assays.
- Western blotting and luciferase reporter assays to validate target genes and signalling pathways.
Main Results:
- miR-124 was significantly down-regulated in GC tissues compared to normal adjacent tissues.
- Forced miR-124 expression suppressed GC cell proliferation, migration, and invasion, and induced cell cycle arrest.
- miR-124 directly targeted JAG1, negatively regulating Notch1 signalling.
- Overexpression of Notch1 intracellular domain repressed miR-124, while Notch1 inhibition by a γ-secretase inhibitor upregulated miR-124.
Conclusions:
- A regulatory feedback loop exists between miR-124 and Notch1 signalling in GC cells.
- The miR-124/Notch axis represents a promising therapeutic strategy for gastric cancer.
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