m6A Methyltransferase, WTAP, Promotes Cancer Progression in Laryngeal Squamous Cell Carcinoma by Regulating PLAU Stability.

ABSTRACT

OBJECTIVE: Laryngeal squamous cell carcinoma (LSCC) is a malignancy originating from laryngeal squamous cell lesions. Wilm's tumor 1-associated protein (WTAP)-mediated N6-methyladenosine (m6A) modification has been verified to stimulate the progression of numerous cancers, except for LSCC. This study was aimed at exploring the role of WTAP and its mechanism of action in LSCC. METHODS: The expression of WTAP and plasminogen activator urokinase (PLAU) mRNAs in LSCC tissues and cells was quantified using qRT-PCR. Western blotting was performed to estimate PLAU levels in LSCC cells. The relationship between WTAP and PLAU was ascertained using luciferase reporter and methylated-RNA immunoprecipitation (Me-RIP) assays. Functionally, the interaction of WTAP with PLAU in LSCC cells was investigated using CCK-8, EdU, and Transwell assays. RESULTS: The expression of WTAP and PLAU was increased in LSCC, and was positively correlated. WTAP regulated PLAU stability in an m6A-dependent manner. WTAP deficiency suppressed the migration, invasion, and proliferation of LSCC cells. Overexpression of PLAU rescued the phenotype induced by WTAP knockdown in vitro. CONCLUSIONS: These results indicate that WTAP mediates the m6A modification of PLAU to accelerate the growth, migration, and invasion of cells in LSCC. To our knowledge, this is the first report to clarify the functions of WTAP in LSCC and the underlying mechanisms in detail. Based on these findings, we suggest that WTAP may serve as a therapeutic target for LSCC.