Chao Song1, Tianwei Chen2,3, Lan He4, Ning Ma2,3, Jian-Ang Li1, Ye-Fei Rong1, Yuan Fang1, Mengmeng Liu5, Dong Xie6,7, Wenhui Lou8. 1. Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. 2. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China. 3. University of the Chinese Academy of Sciences, Shanghai, 200031, China. 4. School of Life Science and Technology, Shanghai Tech University, Shanghai, 201210, China. 5. Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 20032, China. 6. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China. dxie@sibs.ac.cn. 7. University of the Chinese Academy of Sciences, Shanghai, 200031, China. dxie@sibs.ac.cn. 8. Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. lou.wenhui@zs-hospital.sh.cn.
Abstract
BACKGROUND: Protein arginine methyltransferase 1 (PRMT1) is the founding member of the PRMT family of proteins, whose members catalyze methylation of arginine residues in various proteins. Although several studies have reported upregulation of PRMT1 in various cancer types, the expression pattern and the underlying mechanism of PRMT1 action in pancreatic ductal adenocarcinoma (PDAC) are still unclear. METHODS: Immunohistochemistry staining as well as RT-PCR was used to determine the expression pattern of PRMT1 in clinical PDAC samples. Lentivirus packaging and transfection were employed to construct cell lines with PRMT1 overexpression or knockdown. MTT and crystal violet assays were used to determine the proliferation rates of PDAC cells. β-catenin transcription activity was measured using a TOPFlash assay. PRMT1 binding to the promoter region of CTNNB1 was determined by ChIP-qPCR assay. RESULTS: Elevated PRMT1 expression was found in PDAC tissue samples compared to noncancerous normal tissues in 41 patients using a real-time PCR assay and in 90 patients using a tissue microarray (TMA) in conjunction with immunohistochemistry. Analysis of the PRMT1 expression data and PDAC clinical features revealed that PRMT1 expression was significantly correlated with PDAC tumor size and prognosis in postoperative patients. Additional functional experiments revealed that PRMT1 expression promoted the growth of pancreatic cancer-derived cells, both in vitro and in vivo. Mechanistically, we found that PRMT1 increased the cellular β-catenin level. We also found that PRMT1 and β-catenin were co-expressed in TCGA and GTEx datasets containing 370 samples. CONCLUSIONS: Collectively, our study provides novel insight into the expression and function of PRMT1 in PDAC and indicates that PRMT1 may serve as a therapeutic target for treating patients with pancreatic ductal adenocarcinoma.
BACKGROUND:Protein arginine methyltransferase 1 (PRMT1) is the founding member of the PRMT family of proteins, whose members catalyze methylation of arginine residues in various proteins. Although several studies have reported upregulation of PRMT1 in various cancer types, the expression pattern and the underlying mechanism of PRMT1 action in pancreatic ductal adenocarcinoma (PDAC) are still unclear. METHODS: Immunohistochemistry staining as well as RT-PCR was used to determine the expression pattern of PRMT1 in clinical PDAC samples. Lentivirus packaging and transfection were employed to construct cell lines with PRMT1 overexpression or knockdown. MTT and crystal violet assays were used to determine the proliferation rates of PDAC cells. β-catenin transcription activity was measured using a TOPFlash assay. PRMT1 binding to the promoter region of CTNNB1 was determined by ChIP-qPCR assay. RESULTS: Elevated PRMT1 expression was found in PDAC tissue samples compared to noncancerous normal tissues in 41 patients using a real-time PCR assay and in 90 patients using a tissue microarray (TMA) in conjunction with immunohistochemistry. Analysis of the PRMT1 expression data and PDAC clinical features revealed that PRMT1 expression was significantly correlated with PDAC tumor size and prognosis in postoperative patients. Additional functional experiments revealed that PRMT1 expression promoted the growth of pancreatic cancer-derived cells, both in vitro and in vivo. Mechanistically, we found that PRMT1 increased the cellular β-catenin level. We also found that PRMT1 and β-catenin were co-expressed in TCGA and GTEx datasets containing 370 samples. CONCLUSIONS: Collectively, our study provides novel insight into the expression and function of PRMT1 in PDAC and indicates that PRMT1 may serve as a therapeutic target for treating patients with pancreatic ductal adenocarcinoma.
Authors: Rama R Yakubu; Natalie C Silmon de Monerri; Edward Nieves; Kami Kim; Louis M Weiss Journal: Mol Cell Proteomics Date: 2017-01-31 Impact factor: 5.911
Authors: P Andrew Futreal; Lachlan Coin; Mhairi Marshall; Thomas Down; Timothy Hubbard; Richard Wooster; Nazneen Rahman; Michael R Stratton Journal: Nat Rev Cancer Date: 2004-03 Impact factor: 60.716
Authors: Meredith A Miller; Chiu-Yi Liu; Stella R Hartono; Virginia Giuliani; Caleb A Class; Christopher A Bristow; Erika Suzuki; Lionel A Sanz; Guang Gao; Jason P Gay; Ningping Feng; Johnathon L Rose; Hideo Tomihara; Joseph R Daniele; Michael D Peoples; Jennifer P Bardenhagen; Mary K Geck Do; Qing E Chang; Bhavatarini Vangamudi; Christopher Vellano; Haoqiang Ying; Angela K Deem; Kim-Anh Do; Giannicola Genovese; Joseph R Marszalek; Jeffrey J Kovacs; Michael Kim; Jason B Fleming; Ernesto Guccione; Andrea Viale; Anirban Maitra; M Emilia Di Francesco; Timothy A Yap; Philip Jones; Giulio Draetta; Alessandro Carugo; Frederic Chedin; Timothy P Heffernan Journal: Nat Commun Date: 2021-07-30 Impact factor: 14.919