Overexpressing PRMT1 Inhibits Proliferation and Invasion in Pancreatic Cancer by Inverse Correlation of ZEB1

Abstract

Pancreatic cancer (PC) is one of the most malign human cancers, with its underlying molecular mechanisms largely unknown. In this work, we investigated the mechanistic role of protein arginine methyltransferase 1 (PRMT1) gene in PC. Expression of PRMT1 in immortal PC cell lines and clinical human PC tumors was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. In PANC-1 and SW1990 cells, PRMT1 was either downregulated by lentiviral-mediated short hairpin RNA (shRNA) or upregulated by overexpression plasmid. The effects of PRMT1 downregulation or upregulation on PC proliferation and invasion in vitro, and xenograft in vivo, were evaluated. Gene expression of PRMT1 downstream target, zinc finger E-box binding homeobox 1 (ZEB1) was measured in PRMT1-downregulated PC cells. ZEB1 was also upregulated in PRMT1-downregulated PC cells to evaluate its functional role in PRMT1-mediated regulation in PC. PRMT1 was downregulated in both PC cell lines and human tumors. PRMT1 downregulation in PANC-1 and SW1990 cells significantly suppressed cancer proliferation and invasion in vitro and xenograft in vivo. However, PRMT1 overexpression did not have function impact in PC cells. ZEB1 gene expression was suppressed in PRMT1-downregulated PC cells. Subsequently, overexpressing ZEB1 reversed the antitumor effects of PRMT1 downregulation in PC cells. PRMT1 was aberrantly upregulated in PC. PRMT1 inhibition, possibly inversely acting through ZEB1, might be an effective molecular intervention to inhibit PC growth and invasion. © 2018 IUBMB Life, 70(10):1032-1039, 2018.

Keywords: PRMT1; ZEB1; cancer invasion; cancer proliferation; pancreatic cancer; xenograft.