title: Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation.
abstract: Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of symmetrical dimethylation of arginine residues in proteins. WD repeat domain 77 (WDR77), also known as p44, MEP50, or WD45, forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. The molecular mechanisms by which PRMT5 and p44 promote cellular proliferation are unknown.
  
  
  
  Expression of PRMT5 and p44 in lung and prostate cancer cells was silenced and their target genes were identified. The regulation of target genes was validated in various cancer cells during lung development and tumorigenesis. Altered expression of target genes was achieved by ectopic cDNA expression and shRNA-mediated silencing.
  
  
  
  PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression was suppressed by PRMT5 and p44 encoded anti-growth factors and inhibited cell growth when ectopically expressed. In contrast, genes whose expression was enhanced by PRMT5 and p44 encoded growth factors and increased cell growth when expressed. Altered expression of target genes is associated with re-activation of PRMT5 and p44 during lung tumorigenesis.
  
  
  
  Our data provide the molecular basis by which PRMT5 and p44 regulate cell growth and lay a foundation for further investigation of their role in lung tumor initiation.
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, 2012013, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Sheng
authors.affiliation: The Center for Cancer Research and Therapeutic Development, Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Drive, S.W, Atlanta, GA, 30314, USA. zwang@cau.edu.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014157:Transcription Factors; C478359:WDR77 protein, human; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: BTG2; ErbB; FGFR; GLIPR1; Lung cancer; PRMT5; WDR77; p44