title: Screening and functional analysis of differentially expressed genes in EBV-transformed lymphoblasts.
abstract: BACKGROUND
  Epstain-Barr virus (EBV) can transform human B lymphocytes making them immortalized and inducing tumorigenic ability in vitro, but the molecular mechanisms remain unclear. The aim of the present study is to detect and analyze differentially expressed genes in two types of host cells, normal human lymphocytes and coupled EBV-transformed lymphoblasts in vitro using gene chips, and to screen the key regulatory genes of lymphocyte transformation induced by EB virus.
  
  
  METHODS
  Fresh peripheral blood samples from seven healthy donors were collected. EBV was used to transform lymphocytes in vitro. Total RNA was extracted from 7 cases of the normal lymphocytes and transformed lymphoblasts respectively, marked with dihydroxyfluorane after reverse transcription, then hybridized with 4 × 44 K Agilent human whole genome microarray. LIMMA, String, Cytoscape and other softwares were used to screen and analyze differentially expressed genes. Real-time PCR was applied to verify the result of gene expression microarrays.
  
  
  RESULTS
  There were 1745 differentially expressed genes that had been screened, including 917 up-regulated genes and 828 down-regulated genes. According to the results of Generank, String and Cytoscape analyses, 38 genes may be key controlled genes related to EBV-transformed lymphocytes, including 22 up-regulated genes(PLK1, E2F1, AURKB, CDK2, PLCG2, CD80, PIK3R3, CDC20, CDC6, AURKA, CENPA, BUB1B, NUP37, MAD2L1, BIRC5, CDC25A, CCNB1, RPA3, HJURP, KIF2C, CDK1, CDCA8) and 16 down-regulated genes(FYN, CD3D, CD4, CD3G, ZAP70, FOS, HCK, CD247, PRKCQ, ITK, LCP2, CXCL1, CD8A, ITGB5, VAV3, CXCR4), which primarily control biological processes such as cell cycle, mitosis, cytokine-cytokine pathway, immunity response and so on.
  
  
  CONCLUSIONS
  Human lymphocyte transformation induced by EB virus is a complicated process, involving multiple-genes and -pathways in virus-host interactions. Global gene expression profile analysis showed that EBV may transform human B lymphocytes by promoting cell cycle and mitosis, inhibiting cell apoptosis, hindering host immune function and secretion of cytokines.
authors.affiliation: Cancer Research Institute, University of South China, Hunan, 421001, People's Republic of China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Dai
authors.forename: Yunlian
authors.initials: Y
authors.lastname: Tang
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ailan
authors.initials: A
authors.lastname: Cheng
authors.forename: Runliang
authors.initials: R
authors.lastname: Gan
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
mesh_terms: D002461:Cell Line, Transformed / Q000378:metabolism* / Q000821:virology; D002472:Cell Transformation, Viral; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins