Protein arginine methyltransferase 5 is essential for growth of lung cancer cells.
Protein arginine methyltransferase 5 is essential for growth of lung cancer cells.
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DOI：
10.1042/bj20120768
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发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
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作者：
Gu Z;Gao S;Zhang F;Wang Z;Ma W;Davis RE;Wang Z
蛋白质精氨酸甲基转移酶5（PRMT 5）是催化甲基从S-腺苷甲硫氨酸转移到组蛋白或非组蛋白的精氨酸残基的酶，并且参与多种细胞过程。虽然它在一些肿瘤中高度表达，但其在癌症生长中的直接作用尚未得到充分研究。在这项研究中，在人类肺组织样本中，我们发现PRMT 5在肺癌细胞中高度表达，而在良性肺组织中检测不到其表达。沉默PRMT 5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PRMT 5表达也消除了小鼠中肺A549异种移植物的生长。体外和体内研究表明，PRMT 5表达缺失诱导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转导的下调。这些结果表明PRMT 5及其甲基转移酶活性对于肺癌细胞的增殖是必不可少的，并且可以作为治疗肺癌的新靶点。
Protein arginine methyltransferase 5 (PRMT5) is an enzyme that catalyzes transfer of methyl groups from S-adenosyl methionine to the arginine residues of histones or nonhistone proteins and is involved in a variety of cellular processes. Although it is highly expressed in some tumors, its direct role in cancer growth has not been fully investigated. In this 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 downregulation of fibroblast growth factor receptor signaling. 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.