Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States of America.
PLoS One. 2013 Sep 30;8(9):e74710. doi: 10.1371/journal.pone.0074710. eCollection 2013.
Protein arginine methyltransferase-5 (PRMT5) is a Type II arginine methyltransferase that regulates various cellular functions. We hypothesized that PRMT5 plays a role in regulating the growth of human melanoma cells. Immunohistochemical analysis indicated significant upregulation of PRMT5 in human melanocytic nevi, malignant melanomas and metastatic melanomas as compared to normal epidermis. Furthermore, nuclear PRMT5 was significantly decreased in metastatic melanomas as compared to primary cutaneous melanomas. In human metastatic melanoma cell lines, PRMT5 was predominantly cytoplasmic, and associated with its enzymatic cofactor Mep50, but not STAT3 or cyclin D1. However, histologic examination of tumor xenografts from athymic mice revealed heterogeneous nuclear and cytoplasmic PRMT5 expression. Depletion of PRMT5 via siRNA inhibited proliferation in a subset of melanoma cell lines, while it accelerated growth of others. Loss of PRMT5 also led to reduced expression of MITF (microphthalmia-associated transcription factor), a melanocyte-lineage specific oncogene, and increased expression of the cell cycle regulator p27(Kip1). These results are the first to report elevated PRMT5 expression in human melanoma specimens and indicate this protein may regulate MITF and p27(Kip1) expression in human melanoma cells.
蛋白质精氨酸甲基转移酶 5（PRMT5）是一种 II 型精氨酸甲基转移酶，调节各种细胞功能。我们假设 PRMT5 在调节人类黑色素瘤细胞的生长中起作用。免疫组织化学分析表明，与正常表皮相比，PRMT5 在人类黑素细胞痣、恶性黑色素瘤和转移性黑色素瘤中显著上调。此外，与原发性皮肤黑色素瘤相比，转移性黑色素瘤中的核 PRMT5 显著减少。在人类转移性黑色素瘤细胞系中，PRMT5 主要位于细胞质中，并与酶辅因子 Mep50 相关，但与 STAT3 或细胞周期蛋白 D1 无关。然而，对无胸腺小鼠肿瘤异种移植的组织学检查显示 PRMT5 的核和细胞质表达不均匀。通过 siRNA 耗尽 PRMT5 抑制了一部分黑色素瘤细胞系的增殖，而加速了其他细胞系的生长。PRMT5 的缺失也导致小眼相关转录因子（MITF）的表达减少，MITF 是一种黑素细胞系特异性癌基因，细胞周期调节剂 p27（Kip1）的表达增加。这些结果首次报道了 PRMT5 在人类黑色素瘤标本中的表达升高，并表明该蛋白可能调节人类黑色素瘤细胞中的 MITF 和 p27（Kip1）表达。
