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二甲双胍通过Circ_0003214介导的miR-489-3p-ADAM10途径抑制下咽鳞状细胞癌的发展。

Metformin Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma through Circ_0003214-Mediated MiR-489-3p-ADAM10 Pathway.

作者信息

Chen Xiaoqiang, Li Chen, Chen Wei, Lin Shuchun, Yi Xuehan, Lin Qin, Xu Hao, Wang Desheng

机构信息

Department of Otolaryngology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, China.

出版信息

J Oncol. 2021 Jul 13;2021:2265475. doi: 10.1155/2021/2265475. eCollection 2021.

DOI:10.1155/2021/2265475
PMID:34335751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8295003/
Abstract

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 .

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 .

CONCLUSION

Metformin inhibits HSCC progression through the circ_0003214/miR-489-3p/ADAM10 pathway.

摘要

目的

本研究旨在探讨二甲双胍在下咽鳞状细胞癌（HSCC）中的作用及其潜在机制。

方法

使用细胞计数试剂盒-8法、集落形成实验和流式细胞术检测细胞活力、集落形成、细胞凋亡和细胞周期。通过定量实时聚合酶链反应和蛋白质印迹法检测基因表达。通过双荧光素酶报告基因实验或RNA免疫沉淀实验验证靶标关系。进行动物实验以阐明二甲双胍的作用。

结果

二甲双胍抑制HSCC细胞活力和集落形成能力，诱导细胞周期阻滞和凋亡，而circ_0003214过表达减弱了这些作用。Circ_0003214通过靶向miR-489-3p调节含解聚素和金属蛋白酶结构域蛋白10（ADAM10）的表达。此外，miR-489-3p的恢复逆转了circ_0003214的作用，ADAM10的敲低逆转了miR-489-3p抑制介导的效应。此外，二甲双胍通过circ_0003214-miR-489-3p-ADAM10轴阻断肿瘤生长。

结论

二甲双胍通过circ_0003214/miR-489-3p/ADAM10途径抑制HSCC进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/7b60c01c1127/JO2021-2265475.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/62d0fda548fa/JO2021-2265475.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/8a18e93eaacf/JO2021-2265475.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/7b60c01c1127/JO2021-2265475.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/62d0fda548fa/JO2021-2265475.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/674941051f1d/JO2021-2265475.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/94e567e9597d/JO2021-2265475.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/25c7cdf6b937/JO2021-2265475.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/2ef7c6cddc86/JO2021-2265475.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/147805845003/JO2021-2265475.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/8a18e93eaacf/JO2021-2265475.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d56/8295003/7b60c01c1127/JO2021-2265475.008.jpg

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