PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.).
PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.).
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DOI：
10.1371/journal.pone.0074710
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lesinski GB
中科院分区：
文献类型：
--
作者：
Nicholas C;Yang J;Peters SB;Bill MA;Baiocchi RA;Yan F;Sïf S;Tae S;Gaudio E;Wu X;Grever MR;Young GS;Lesinski GB
蛋白质精氨酸甲基转移酶-5（PRMT 5）是调节多种细胞功能的II型精氨酸甲基转移酶。我们假设PRMT 5在调节人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，PRMT 5在人黑色素细胞痣、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PRMT 5显著降低。在人转移性黑色素瘤细胞系中，PRMT 5主要是细胞质的，并与其酶辅因子Mep 50相关，但不与STAT 3或细胞周期蛋白D1相关。然而，无胸腺小鼠的肿瘤异种移植物的组织学检查显示异质性核和细胞质PRMT 5表达。通过siRNA消耗PRMT 5抑制了黑色素瘤细胞系亚群的增殖，同时加速了其他细胞系的生长。PRMT 5的缺失还导致MITF（小眼症相关转录因子）（一种黑素细胞谱系特异性致癌基因）的表达减少，以及细胞周期调节因子p27 Kip 1的表达增加。这些结果首次报道了PRMT 5在人黑色素瘤标本中的表达升高，并表明这种蛋白质可能调节人黑色素瘤细胞中MITF和p27 Kip 1的表达。
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 p27Kip1. These results are the first to report elevated PRMT5 expression in human melanoma specimens and indicate this protein may regulate MITF and p27Kip1 expression in human melanoma cells.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
7.3
作者：
Andreu-Pérez P;Esteve-Puig R;de Torre-Minguela C;López-Fauqued M;Bech-Serra JJ;Tenbaum S;García-Trevijano ER;Canals F;Merlino G;Avila MA;Recio JA
通讯作者：
Recio JA
影响因子：
4.8
作者：
Friesen, WJ;Wyce, A;Dreyfuss, G
通讯作者：
Dreyfuss, G
影响因子：
14.9
作者：
He, Wei;Ma, Xiaoyan;Hang, Haiying
通讯作者：
Hang, Haiying
影响因子：
64.8
作者：
Carreira, S;Goodall, J;Goding, CR
通讯作者：
Goding, CR