The RNA N6-Methyladenosine Demethylase FTO Promotes Head and Neck Squamous Cell Carcinoma Proliferation and Migration by Increasing CTNNB1.

OBJECTIVE

In this study, we aimed to investigate the role of RNA N6-methyladenosine demethylase fat mass and obesity-associated protein () in head and neck squamous cell carcinoma (HNSCC).

METHODS

Clinical data downloaded from The Cancer Genome Atlas (TCGA) database were used to analyze the relationship between mRNA levels of , and , and the overall survival in cancer and para-cancer datasets. expression in tumor and normal tissues was compared using immunohistochemistry, and its relationship with overall survival was analyzed based on the Kaplan-Meier method. The FaDu cell line with high levels was chosen from five HNSCC cell lines for further experiments. was verified as an oncogene in HNSCC by in vitro loss-of-function and overexpression studies, cell proliferation assay, wound healing assay, and identification of expression changes of epithelial-mesenchymal transition (EMT)-related markers. Catenin beta 1 () was confirmed as a downstream target gene of with additional methods like the GEPIA online tool, qRT-PCR, Western blotting, and dot blot assay.

RESULTS

We found that expression was significantly upregulated in HNSCC datasets and tissues. Increased expression indicated a trend towards poor prognosis and was found to promote disease proliferation and migration. Mechanistically, cell proliferation assay, wound healing assay, and identification of expression changes of EMT-related markers demonstrated that could act as an oncogene in HNSCC. expression was significantly correlated with expression. Moreover, it exerted a tumorigenic effect by increasing expression in an mA-dependent manner.

CONCLUSION

promotes head and neck squamous cell carcinoma proliferation and migration by increasing in an mA-dependent manner.