title: Network signatures of cellular immortalization in human lymphoblastoid cell lines.
abstract: Human lymphoblastoid cell line (LCL) has been used as an in vitro cell model in genetic and pharmacogenomic studies, as well as a good model for studying gene expression regulatory machinery using integrated genomic analyses. In this study, we aimed to identify biological networks of LCL immortalization from transcriptomic profiles of microRNAs and their target genes in LCLs. We first selected differentially expressed genes (DEGs) and microRNAs (DEmiRs) between early passage LCLs (eLCLs) and terminally differentiated late passage LCLs (tLCLs). The in silico and correlation analysis of these DEGs and DEmiRs revealed that 1098 DEG-DEmiR pairs were found to be positively (n=591 pairs) or negatively (n=507 pairs) correlated with each other. More than 41% of DEGs are possibly regulated by miRNAs in LCL immortalizations. The target DEGs of DEmiRs were enriched for cellular functions associated with apoptosis, immune response, cell death, JAK-STAT cascade and lymphocyte activation while non-miRNA target DEGs were over-represented for basic cell metabolisms. The target DEGs correlated negatively with miR-548a-3p and miR-219-5p were significantly associated with protein kinase cascade, and the lymphocyte proliferation and apoptosis, respectively. In addition, the miR-106a and miR-424 clusters located in the X chromosome were enriched in DEmiR-mRNA pairs for LCL immortalization. In this study, the integrated transcriptomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Sung-Mi
authors.initials: SM
authors.lastname: Shim
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Jung
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Nam
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Mee-Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Jun-Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.affiliation: Division of Brain Diseases, Center for Biomedical Science, Korea National Institute of Health, Osong 363-951, Republic of Korea. Electronic address: jaepiljeon@hanmail.net.
authors.forename: Jae-Pil
authors.initials: JP
authors.lastname: Jeon
mesh_terms: D002461:Cell Line, Transformed; D041321:Chromosomes, Human, X / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Integrated transcriptomic analysis; LCL; mRNA; miRNA