Overexpressing PRMT1 Inhibits Proliferation and Invasion in Pancreatic Cancer by Inverse Correlation of ZEB1
Overexpressing PRMT1 Inhibits Proliferation and Invasion in Pancreatic Cancer by Inverse Correlation of ZEB1
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DOI：
10.1002/iub.1917
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发表时间：
2018-10-01
期刊：
影响因子：
4.6
通讯作者：
Dong, Yangyang
中科院分区：
文献类型：
--
作者：
Lin, Zhibin;Chen, Yao;Dong, Yangyang
胰腺癌(PC)是人类最恶性的癌症之一，其潜在的分子机制尚不清楚。本研究旨在探讨蛋白精氨酸甲基转移酶1(PRMT1)基因在前列腺癌发病机制中的作用。用实时定量聚合酶链式反应(qRT-PCR)和免疫印迹法检测PRMT1在永生化PC细胞系和临床人PC肿瘤中的表达。在PANC-1和SW1990细胞中，PRMT1要么被慢病毒介导的短发夹状RNA(ShRNA)下调，要么被高表达载体上调。观察PRMT1表达下调或上调对PC体外增殖和侵袭的影响，以及体内异种移植的影响。在PRMT1下调的PC细胞中检测PRMT1下游靶基因锌指E盒结合同源盒1(ZEB1)的基因表达。在PRMT1下调的PC细胞中，ZEB1也被上调，以评估其在PRMT1介导的PC调控中的功能作用。PRMT1在PC细胞系和人类肿瘤中均下调。PANC-1和SW1990细胞中PRMT1的下调在体外和体内均能显著抑制肿瘤的增殖和侵袭。然而，PRMT1的过表达对PC细胞的功能没有影响。在PRMT1下调的PC细胞中，ZEB1基因的表达受到抑制。随后，过表达ZEB1逆转了PRMT1在PC细胞中下调的抗肿瘤作用。PRMT1在PC中异常上调。抑制PRMT1可能通过ZEB1起反向作用，可能是抑制PC生长和侵袭的有效分子干预措施。(C)2018年IUBMB Life，70(10)：1032-1039,2018
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. (c) 2018 IUBMB Life, 70(10):1032-1039, 2018