PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.).
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...
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doaj-7080494a75d84abfb87b667153a504732020-11-25T00:42:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7471010.1371/journal.pone.0074710PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.).Courtney NicholasJennifer YangSara B PetersMatthew A BillRobert A BaiocchiFengting YanSaïd SïfSookil TaeEugenio GaudioXin WuMichael R GreverGregory S YoungGregory B LesinskiProtein 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.http://europepmc.org/articles/PMC3786975?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Courtney Nicholas Jennifer Yang Sara B Peters Matthew A Bill Robert A Baiocchi Fengting Yan Saïd Sïf Sookil Tae Eugenio Gaudio Xin Wu Michael R Grever Gregory S Young Gregory B Lesinski |
spellingShingle |
Courtney Nicholas Jennifer Yang Sara B Peters Matthew A Bill Robert A Baiocchi Fengting Yan Saïd Sïf Sookil Tae Eugenio Gaudio Xin Wu Michael R Grever Gregory S Young Gregory B Lesinski PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.). PLoS ONE |
author_facet |
Courtney Nicholas Jennifer Yang Sara B Peters Matthew A Bill Robert A Baiocchi Fengting Yan Saïd Sïf Sookil Tae Eugenio Gaudio Xin Wu Michael R Grever Gregory S Young Gregory B Lesinski |
author_sort |
Courtney Nicholas |
title |
PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.). |
title_short |
PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.). |
title_full |
PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.). |
title_fullStr |
PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.). |
title_full_unstemmed |
PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.). |
title_sort |
prmt5 is upregulated in malignant and metastatic melanoma and regulates expression of mitf and p27(kip1.). |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3786975?pdf=render |
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