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

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. The 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 cell apoptosis. Furthermore, wound 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) was proved to be a putative target for miR-25-5p. The role of NEDD9 in inhibiting OSCC cell 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.

NEDD9 overexpression: Prognostic and guidance value in acute myeloid leukaemia

“…MiR ‐ 25 ‐ 5p directly targeting NEDD9 was found in oral squamous cell carcinoma and colorectal cancer. 38 , 39 Moreover, NEDD9 expression regulated by miR ‐ 145 was revealed in lung cancer, pancreatic cancer, renal cell carcinoma, prostate cancer and glioblastoma. 40 , 41 , 42 , 43 , 44 Additionally, NEDD9 expression negatively associated with miR ‐ 125a / b was shown in pancreatic cancer, lung adenocarcinoma and melanoma.…”

CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

“…The melatonin is further metabolized into 6-hydroxymelatonin (6OH-MEL) by human cytochrome P450 family [ 4 ]. Evidence shows that various biological properties of melatonin, such as the circadian clock [ 5 , 6 , 7 ], sleep regulation [ 8 , 9 ], anti-inflammatory properties [ 10 , 11 , 12 ], immune modulation [ 13 , 14 , 15 ], and anti-cancer activities [ 16 , 17 , 18 ], have been well revealed. Nevertheless, the clinical and immunological function of the cytochrome P450 family in cancer remains unclear.…”

Long noncoding RNA uc003pxg.1 regulates endothelial cell proliferation and migration via miR‑25‑5p in coronary artery disease

“…The expression levels of miRNAs were verified in HUVECs following transfection with si- uc003pxg.1 , as well as in PBMCs from clinical samples by RT-qPCR. miR-25-5p , which is associated with cell proliferation and migration, was selected for further analysis according to previous studies ( 29 , 30 ). The results demonstrated that the expression levels of miR-25-5p were significantly upregulated following uc003pxg.1 knockdown compared with those in the control cells ( Fig.…”