title: MicroRNA signatures associated with immortalization of EBV-transformed lymphoblastoid cell lines and their clinical traits.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are negative regulators of gene expression that play important roles in cell processes such as proliferation, development and differentiation. Recently, it has been reported that miRNAs are related to development of carcinogenesis. The aim of this study was to identify miRNAs associated with terminal immortalization of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line (LCL) and associated clinical traits.
  
  
  METHODS
  Hence, we performed miRNA microarray approach with early- (p6) and late-passage (p161) LCLs.
  
  
  CONCLUSIONS
  Microarray data showed that nine miRNAs (miR-20b*, miR-28-5p, miR-99a, miR-125b, miR-151-3p, miR-151:9.1, miR-216a, miR-223* and miR-1296) were differentially expressed in most LCLs during long-term culture. In particular, miR-125b was up-regulated in all the tested late-passage LCLs. miR-99a, miR-125b, miR-216a and miR-1296 were putative negative regulators of RASGRP3, GPR160, PRKCH and XAF1, respectively, which were found to be differentially expressed in LCLs during long-term culture in a previous study. Linear regression analysis showed that miR-200a and miR-296-3p correlated with triglyceride and HbA1C levels, respectively, suggesting that miRNA signatures of LCLs could provide information on the donor's health. In conclusion, our study suggests that expression changes of specific miRNAs may be required for terminal immortalization of LCLs. Thus, differentially expressed miRNAs would be a potential marker for completion of cell immortalization during EBV-mediated tumorigenesis.
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul, South Korea.
authors.forename: J-E
authors.initials: JE
authors.lastname: Lee
authors.forename: E-J
authors.initials: EJ
authors.lastname: Hong
authors.forename: H-Y
authors.initials: HY
authors.lastname: Nam
authors.forename: J-W
authors.initials: JW
authors.lastname: Kim
authors.forename: B-G
authors.initials: BG
authors.lastname: Han
authors.forename: J-P
authors.initials: JP
authors.lastname: Jeon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D016014:Linear Models; D008214:Lymphocytes / Q000378:metabolism* / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D020663:ras Guanine Nucleotide Exchange Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C555417:GPR160 protein, human; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; C413212:RASGRP3 protein, human; D043562:Receptors, G-Protein-Coupled; C417551:XAF1 protein, human; D020663:ras Guanine Nucleotide Exchange Factors; C081975:protein kinase C eta; D011493:Protein Kinase C