PRMT5 encourages cell migration and metastasis of tongue squamous cell carcinoma through methylating ΔNp63α

Abstract

Tongue squamous cell carcinoma (TSCC) is a common oral malignancy prone to metastasis, whose underlying mechanism remains obscure. Here, we report the oncogenic roles of protein arginine methyltransferase 5 (PRMT5) in TSCC via inhibiting transcription factor ΔNp63α. We found that PRMT5 physically interacts with ΔNp63α, resulting in impairment of ΔNp63α-mediated transcriptional regulation. Further investigation revealed that PRMT5 is significantly upregulated in late stages of TSCC and correlated to poor prognosis. On the other hand, inhibition on ΔNp63α contributes to PRMT5-induced migration and metastasis of TSCC cells. Mechanistically, PRMT5 mediates methylation of ΔNp63α at Arg561, which facilitates CDK1-mediated phosphorylation of ΔNp63α and results in weakened DNA binding of this transcription factor. Consequently, ΔNp63α-mediated suppression on cell migration is attenuated in TSCC. Inhibition of PRMT5 efficiently restrain metastasis of TSCC cells in vivo. Our study is helpful to illuminate the molecular mechanism of TSCC metastasis and to provide a new therapeutic strategy for this malignancy.