Prmt2 Beta, A C-Terminal Splice Variant Of Prmt2, Inhibits The Growth Of Breast Cancer Cells

Our previous study reported several alternative splicing variants of arginine N-methyltransferase 2 (PRMT2), which lose different exons in the C-terminals of the wild-type PRMT2 gene. Particularly, due to frame-shifting, PRMT2 beta encodes a novel amino acid sequence at the C-terminus of the protein, the function of which is not understood. In the present study, we determined the role of PRMT2 beta in breast cancer cell proliferation, apoptosis and its effect on the Akt signaling pathway. Stable breast cancer MCF7 cell line with lentivirus-mediated PRMT2 beta overexpression was obtained after selection by puromycin for 2 weeks. The effect of lentivirus-mediated PRMT2 beta overexpression on breast cancer cellular oncogenic properties was evaluated by MTT, colony formation, cell cycle analysis and apoptosis assays in MCF7 cells. Luciferase activity assay and western blot analysis were performed to characterize the effects of PRMT2 beta on cyclin D1 promoter activities and the Akt signaling pathway. Tissue microarray was performed to investigate the association of PRMT2 beta with breast cancer progression. Lentivirus-mediated PRMT2 beta overexpression suppressed the cell proliferation and colony formation of breast cancer MCF7 cells. PRMT2 beta overexpression induced cell cycle arrest and apoptosis of MCF7 cells. Furthermore, PRMT2 beta was revealed to suppress the transcription activity of the cyclin D1 promoter, and PRMT2 beta was also found to inhibit cyclin D1 expression via the suppression of Akt/GSK-3 beta signaling in breast cancer cells. Clinically, it was revealed that PRMT2 beta expression was negatively correlated with human epidermal growth factor receptor 2 (HER2) (p=0.033) in breast tumors. Our results revealed that PRMT2 beta, a novel splice variant of PRMT2, plays potential antitumor effect by suppressing cyclin D1 expression and inhibiting Akt signaling activity. This also opens a new avenue for treating breast cancer.