Abstract
PRMT5 (protein arginine methyltransferase 5) is an enzyme that catalyses transfer of methyl groups from S-adenosyl methionine to the arginine residues of histones or non-histone proteins and is involved in a variety of cellular processes. Although it is highly expressed in some tumours, its direct role in cancer growth has not been fully investigated. In the present 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 down-regulation of fibroblast growth factor receptor signalling. 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / enzymology*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Animals
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Carcinoma, Squamous Cell / enzymology
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology
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Cell Line, Tumor
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Cell Proliferation
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Gene Expression Profiling
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Gene Silencing
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Humans
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Lung / enzymology*
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Lung / metabolism
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Lung / pathology
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Lung Neoplasms / enzymology*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Nude
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Mutant Proteins / antagonists & inhibitors
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Mutant Proteins / metabolism
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neoplasm Transplantation
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Protein-Arginine N-Methyltransferases / antagonists & inhibitors
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Protein-Arginine N-Methyltransferases / genetics
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Protein-Arginine N-Methyltransferases / metabolism*
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RNA, Small Interfering
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Receptor, Fibroblast Growth Factor, Type 3 / antagonists & inhibitors
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Receptor, Fibroblast Growth Factor, Type 3 / genetics
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Receptor, Fibroblast Growth Factor, Type 3 / metabolism
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Signal Transduction
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Small Cell Lung Carcinoma / enzymology
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Small Cell Lung Carcinoma / metabolism
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Small Cell Lung Carcinoma / pathology
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Tumor Burden
Substances
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Mutant Proteins
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Neoplasm Proteins
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RNA, Small Interfering
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Recombinant Proteins
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PRMT5 protein, human
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Protein-Arginine N-Methyltransferases
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FGFR3 protein, human
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Receptor, Fibroblast Growth Factor, Type 3