Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Biochem J. 2012 Sep 1;446(2):235-41. doi: 10.1042/BJ20120768.
PRMT5 (protein arginine methyltransferase 5) is an enzyme that catalyses transfer of methyl groups from S-adenosyl methionine to the arginine residues of histones or non-histone proteins and is involved in a variety of cellular processes. Although it is highly expressed in some tumours, its direct role in cancer growth has not been fully investigated. In the present study, in human lung tissue samples we found that PRMT5 was highly expressed in lung cancer cells, whereas its expression was not detectable in benign lung tissues. Silencing PRMT5 expression strongly inhibited proliferation of lung adenocarcinoma A549 cells in tissue culture, and silencing PRMT5 expression in A549 cells also abolished growth of lung A549 xenografts in mice. In vitro and in vivo studies showed that the cell growth arrest induced by loss of PRMT5 expression was partially attributable to down-regulation of fibroblast growth factor receptor signalling. These results suggest that PRMT5 and its methyltransferase activity is essential for proliferation of lung cancer cells and may serve as a novel target for the treatment of lung cancer.
PRMT5（蛋白质精氨酸甲基转移酶 5）是一种酶，能够催化 S-腺苷甲硫氨酸的甲基转移到组蛋白或非组蛋白蛋白质的精氨酸残基上，并参与多种细胞过程。尽管它在一些肿瘤中高度表达，但它在癌症生长中的直接作用尚未得到充分研究。在本研究中，我们在人肺组织样本中发现，PRMT5 在肺癌细胞中高度表达，而在良性肺组织中则检测不到其表达。沉默 PRMT5 表达强烈抑制肺腺癌 A549 细胞在组织培养中的增殖，并且沉默 A549 细胞中的 PRMT5 表达也消除了 A549 肺异种移植瘤在小鼠中的生长。体外和体内研究表明，PRMT5 表达缺失引起的细胞生长停滞部分归因于成纤维细胞生长因子受体信号通路的下调。这些结果表明，PRMT5 及其甲基转移酶活性对于肺癌细胞的增殖是必需的，并且可能成为治疗肺癌的新靶标。
