PRMT5 Is Upregulated in Malignant and Metastatic Melanoma and Regulates Expression of MITF and p27Kip1

• Published in: PloS one Vol. 8; no. 9; p. e74710
• Main Authors: Nicholas, Courtney, Yang, Jennifer, Peters, Sara B., Bill, Matthew A., Baiocchi, Robert A., Yan, Fengting, Sïf, Saïd, Tae, Sookil, Gaudio, Eugenio, Wu, Xin, Grever, Michael R., Young, Gregory S., Lesinski, Gregory B.
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 30-09-2013
• Subjects: Apoptosis; Arginine; Biochemistry; Biotechnology; Cell cycle; Cell growth; Cyclin D1; Cyclin-dependent kinase inhibitor p27; Enzymes; Epidermis; Gene expression; Hematology; Internal medicine; Kinases; Leukemia; Lung cancer; Lymphoma; Medicine; Melanoma; Metastases; Metastasis; Microphthalmia-associated transcription factor; Oncology; Prostate; Protein arginine methyltransferase; Proteins; Signal transduction; siRNA; Skin cancer; Stat3 protein; Transcription factors; Xenografts; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0074710

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.