AUTHOR=Wang Yanling , Tao Bo , Li Jiaying , Mao Xiaoqun , He Wei , Chen Qinbiao 

TITLE=Melatonin Inhibits the Progression of Oral Squamous Cell Carcinoma via Inducing miR-25-5p Expression by Directly Targeting NEDD9

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.543591

DOI=10.3389/fonc.2020.543591

ISSN=2234-943X

ABSTRACT=Melatonin exerts anti-cancer roles in various types of cancers. However, to the best of our knowledge, its role in oral squamous cell carcinoma (OSCC) is unknown. The present study aimed to investigate the role of melatonin and its underlying mechanism in OSCC. MTT, colony formation, wound healing and transwell invasion assays proved that melatonin played anti-tumor effects in OSCC cells by inhibiting cell viability, proliferation, migration and invasion in a concentration dependent manner. RT-qPCR analysis showed that miR-25-5p was significantly upregulated after melatonin treatment. Further, miR-25-5p might be involved in melatonin-induced inhibitory effects on the biological behavior of OSCC. The expression of miR-25-5p was decreased in tumor tissues and OSCC cells detected by RT-qPCR. MTT assay, colony formation assay and TUNEL staining indicated miR 25 5p overexpression inhibited OSCC cell viability, proliferation and induced OSCC cells apoptosis. Furthermore, would healing, transwell invasion assay and animal experiments suggested that miR-25-5p might exert suppressive effects on the migration, invasion and tumor formation of OSCC cells. While, miR-25-5p knockdown exhibited the opposite effects in OSCC cells. Bioinformatics analysis, western blot analysis and luciferase reporter assay suggested that neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) might be a putative target for miR-25-5p. The role of NEDD9 in inhibiting OSCC cells proliferation, invasion and migration was verified with NEDD9 siRNA transfection. Thus, melatonin exerted anti-proliferative, anti-invasive and anti-migrative effects on OSCC via miR-25-5p/NEDD9 pathway. Melatonin could be applied as a potential novel drug on treating OSCC.