1. Network signatures of cellular immortalization in human lymphoblastoid cell lines
- Author
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Sung-Mi Shim, Jun-Woo Kim, Hye Ryun Kim, Hye-Young Nam, Mee-Hee Lee, Jae-Pil Jeon, So-Young Jung, and Bok-Ghee Han
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,In silico ,Cell ,Biophysics ,Lymphocyte proliferation ,Biology ,Biochemistry ,Transcriptome ,Gene expression ,microRNA ,otorhinolaryngologic diseases ,medicine ,Humans ,Gene Regulatory Networks ,RNA, Messenger ,Molecular Biology ,Gene ,Cell Line, Transformed ,Genetics ,Chromosomes, Human, X ,Gene Expression Regulation, Leukemic ,Cell growth ,Cell Biology ,Cell biology ,MicroRNAs ,stomatognathic diseases ,medicine.anatomical_structure - Abstract
Highlights: •We identified network signatures of LCL immortalization from transcriptomic profiles. •More than 41% of DEGs are possibly regulated by miRNAs in LCLs. •MicroRNA target genes in LCLs are involved in apoptosis and immune-related functions. •This approach is useful to find functional miRNA targets in specific cell conditions. -- 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 activationmore » 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.« less
- Published
- 2013
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