PRMT2β, a C-terminal splice variant of PRMT2, inhibits the growth of breast cancer cells.

Abstract

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, PRMT2β 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 PRMT2β in breast cancer cell proliferation, apoptosis and its effect on the Akt signaling pathway. Stable breast cancer MCF7 cell line with lentivirus-mediated PRMT2β overexpression was obtained after selection by puromycin for 2weeks. The effect of lentivirus-mediated PRMT2β 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 PRMT2β on cyclinD1 promoter activities and the Akt signaling pathway. Tissue microarray was performed to investigate the association of PRMT2β with breast cancer progression. Lentivirus-mediated PRMT2β overexpression suppressed the cell proliferation and colony formation of breast cancer MCF7 cells. PRMT2β overexpression induced cell cycle arrest and apoptosis of MCF7 cells. Furthermore, PRMT2β was revealed to suppress the transcription activity of the cyclinD1 promoter, and PRMT2β was also found to inhibit cyclinD1 expression via the suppression of Akt/GSK-3β signaling in breast cancer cells. Clinically, it was revealed that PRMT2β expression was negatively correlated with human epidermal growth factor receptor2 (HER2) (p=0.033) in breast tumors. Our results revealed that PRMT2β, a novel splice variant of PRMT2, plays potential antitumor effect by suppressing cyclinD1 expression and inhibiting Akt signaling activity. This also opens a new avenue for treating breast cancer.