Methyltransferase-like 3-induced N6-methyladenosine upregulation promotes oral squamous cell carcinoma by through p38.

Background Oral squamous cell carcinoma (OSCC), a main type of squamous cell cancer, is associated with considerable morbidity and mortality. Recent reports suggested methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification to be an essential regulator in the fate determination of stem cells. However, the functional significance of METTL3 in OSCC remains largely unknown. Methods METTL3 expression was examined in OSCC patient samples, followed by correlation analysis against clinical tumor features. Functional assays, such as assessment of surface marker expression, colony forming, BrdU incorporation, tumor xenograft assay, as well as m6A dot blot, were conducted to study the impact of METTL3 knock down (KD) in OSCC cells. Results High METTL3 expression was positively correlated with more severe clinical features of OSCC tumors. METTL3 KD caused impairment of stem-like capacities in OSCC cells, such as tumorigenicity in vivo as well as colony forming ability in vitro. Furthermore, METTL3-KD and cycloleucine, a methylation inhibitor, decreased m6A levels and down-regulated p38 expression in OSCC cells. On the other hand, the impaired cell proliferation capacity of OSCC cells after METTL3-KD was restored by exogenous expression of p38. Conclusion Our findings identified m6A methyltransferase METTL3 as a key element in the regulation of tumorigenesis in OSCC.