MicroRNA-425 promotes the development of lung adenocarcinoma via targeting A disintegrin and metalloproteinases 9 (ADAM9)

Ruibao Liu, Fang Wang, Yanchun Guo, Jianmei Yang, Shaoping Chen, Xin Gao, Xunguo Wang Department of Oncology, Dongying People’s Hospital, Dongying, Shandong 257091, People’s Republic of China Purpose: We aimed to investigate the roles of microRNA-425 (miR-425) in lung adenocarcinoma, as well as its possible regulatory mechanism.Materials and methods: The miR-425 expression in lung adenocarcinoma tissues and cells was determined. The regulatory relationship between miR-425 and IL-6/STAT3 signaling was investigated. In addition, miR-425 was downexpressed in H1299 cells, and its effects on cell proliferation and apoptosis were determined. Furthermore, the target relationship between miR-425 and A disintegrin and metalloproteinases 9 (ADAM9) in lung adenocarcinoma cells was explored.Results: The miR-425 was significantly downregulated in lung adenocarcinoma tissues and cells and was markedly inhibited by IL-6/STAT3 signaling. In addition, miR-425 expression was successfully overexpressed by transfection with pre-miR-425. Overexpression of miR-425 decreased the proliferation and colony formation of H1299 cells and promoted cell apoptosis markedly. Moreover, ADAM9 was revealed as a target of miR-425, and ADAM9 expression was negatively regulated by miR-425.Conclusion: Our findings indicate that downregulation of miR-425 caused by IL-6/STAT3 signaling leads to loss of ADAM9 targeting, results in enhanced ADAM9 expression, and contributes to the development of lung adenocarcinoma. Thus, increasing miR-425 may be a promising therapeutic strategy for this disease. Keywords: lung adenocarcinoma, microRNA-425, IL-6/STAT3 signaling, proliferation, apoptosis, A disintegrin and metalloproteinases 9&nbsp