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

Abstract

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.

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

“…Recent reports have revealed the relationship between various cancers and PRMT1, which is overexpressed in breast cancer, bladder cancer and lung cancer [17][18][19][20].. Notably, PRMT1 was recently reported to be upregulated through miR-503 in HCC [21], and PRMT1 may promote the proliferation and metastasis of HCC cells in vitro [13].…”

Nonclassical nuclear localization signals mediate nuclear import of CIRBP

“…Alteration in arginine methylation of RG/RGG-containing proteins is associated with a plethora of neurodegenerative diseases and cancers (11,13,48,63,(78)(79)(80). In line with this, PRMT1 mRNA levels are increased in several cancer cells and tumors (81)(82)(83). Moreover, PRMT1 has been shown to regulate epithelial-mesenchymal transition, cancer cell migration, and invasion, which are hallmarks of cancer progression and metastasis (84).…”

Hepatocellular Protein Arginine Methyltransferase 1 Suppresses Alcohol‐Induced Hepatocellular Carcinoma Formation by Inhibition of Inducible Nitric Oxide Synthase

“…PRMT1 is known to promote proliferation of many cancer cell lines in vitro and in vivo , ( 16,17,20‐22 ) including hepatoma cell lines. We confirmed that PRMT1 inhibition using a small molecule inhibitor, protein arginine methyltransferase inhibitor, reduced hepatoma cell proliferation under normal conditions.…”