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Metformin Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma through Circ_0003214-Mediated
Xiaoqiang Chen1, Chen Li1, Wei Chen1
1Department of Otolaryngology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, China.
Purpose:
This study aims to explore the function of metformin in hypopharyngeal squamous cell carcinoma (HSCC) and the underlying mechanism.
Methods:
Cell viability, colony formation, cell apoptosis, and cell cycle were investigated using cell counting kit-8 assay, colony formation, and flow cytometry assay. Gene expression was detected by quantitative real-time polymerase chain reaction and western blot. The target relationship was validated by dual-luciferase reporter assay or RNA immunoprecipitation assay. An animal study was implemented to clarify the effect of metformin in vivo.
Results:
Metformin suppressed HSCC cell viability and colony formation ability and induced cell cycle arrest and apoptosis, and circ_0003214 overexpression weakened these effects. Circ_0003214 regulated A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression via targeting miR-489-3p. Besides, miR-489-3p restoration reversed the role of circ_0003214, and ADAM10 knockdown reversed miR-489-3p inhibition-mediated effect. Moreover, metformin blocked tumor growth via the circ_0003214-miR-489-3p-ADAM10 axis in vivo.
Conclusion:
Metformin inhibits HSCC progression through the circ_0003214/miR-489-3p/ADAM10 pathway.
Insights
Metformin inhibits hypopharyngeal squamous cell carcinoma (HSCC) progression by targeting the circ_0003214/miR-489-3p/ADAM10 pathway. This finding offers a potential therapeutic strategy for HSCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive cancer with limited treatment options.
- Understanding the molecular mechanisms underlying HSCC progression is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the anti-cancer effects of metformin in HSCC.
- To elucidate the underlying molecular mechanism involving circ_0003214, miR-489-3p, and ADAM10.
Main Methods:
- Cell viability, colony formation, apoptosis, and cell cycle assays were performed.
- Gene and protein expression levels were analyzed using qRT-PCR and Western blot.
- In vivo studies in animal models were conducted to validate findings.
Main Results:
- Metformin suppressed HSCC cell viability and colony formation, inducing cell cycle arrest and apoptosis.
- The circ_0003214/miR-489-3p/ADAM10 axis was identified as a key pathway regulated by metformin.
- Metformin demonstrated tumor growth inhibition in vivo via this pathway.
Conclusions:
- Metformin exhibits anti-cancer properties in HSCC by modulating the circ_0003214/miR-489-3p/ADAM10 pathway.
- This pathway represents a potential therapeutic target for HSCC treatment.
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