PRMT1 expression is elevated in head and neck cancer and inhibition of protein arginine methylation by adenosine dialdehyde or PRMT1 knockdown downregulates proliferation and migration of oral cancer cells.

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Protein arginine methylation is a post-translational modification that has been implicated in signal transduction, gene transcription, DNA repair and RNA processing. Overexpression or deregulation of protein arginine methyltransferases (PRMTs) have been reported to be associated with various cancers but have not been studied in head and neck cancer (HNC). We investigated the involvement of the modification in HNC using oral cancer cell lines (SAS, OECM-1 and HSC-3) and an immortalized normal oral cells (S-G). The expression levels of the predominant PRMT1 were generally consistent with the levels of asymmetric dimethylarginine (ADMA), highest in SAS and OECM1, then S-G and low in HSC-3. Upon the treatment with an indirect methyltransferase inhibitor adenosine dialdehyde (AdOx), the ADMA levels in SAS and OECM1, but not that in S-G and HSC-3, decreased significantly. SAS and OECM with high ADMA levels grew faster than HSC-3 and S-G. The growth rate of the fast growing SAS and OECM, but not that of the other two cell lines, decreased significantly upon AdOx treatment. The migration activity of SAS and HSC-3, two cell lines with migration ability also decreased after the AdOx treatment. Immunohistochemical analyses of specimens from typical HNC patients showed strong PRMT1 expression in the tumor cells compared with neighboring normal cells. Knockdown of PRMT1 in SAS cells decreased the levels of PRMT1 and ADMA-containing proteins significantly. These cells showed decreased growth rate, reduced migration activity but increased expression of the epithelial marker E-cadherin. The present study thus provides fundamental background for evaluation of the PRMT1 gene as the therapeutic targets of HNC.