Protein arginine methyltransferase 5 is essential for growth of lung cancer cells.
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.
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zhongping
Z
Gu
Shen
S
Gao
Fahao
F
Zhang
Zhiqiang
Z
Wang
Wencai
W
Ma
Richard E
RE
Davis
Zhengxin
Z
Wang
D000230:Adenocarcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden
D050505:Mutant Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3