Biochemical and Biophysical Research Communications, 2013, 01, 438─446

Network signatures of cellular immortalization in human lymphoblastoid cell lines

Sung-Mi Shim, SoYoung Jung, HyeYoung Nam, HyeRyun Kim, Me-Hee Lee, JunWoo Kim, BokGhee Han, JaePil Jeon

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 tranomic 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 tranomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.

• ISBN or ISSN: 0006-291x

• 본 연구는 질병관리본부 연구개발과제(과제번호 2013-NG74001-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2013-NG74001-00) by Research of Korea Centers for Disease Control and Prevention.