Statin-induced changes in gene expression in EBV-transformed and native B-cells
Eugene Bolotin1, Angela Armendariz, Kyungpil Kim
1Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
Human Molecular Genetics
|November 2, 2013
Summary
Human lymphoblastoid cell lines (LCLs) are useful for studying statin effects on cholesterol metabolism. However, Epstein-Barr Virus (EBV) transformation may alter drug responses related to cell cycle and apoptosis.
Area of Science:
- Pharmacogenomics
- Cell Biology
- Virology
Background:
- Human lymphoblastoid cell lines (LCLs), derived from Epstein-Barr Virus (EBV) transformed B-lymphocytes, are widely used to study genetic influences on disease and drug response.
- Previous studies utilized LCLs to investigate genetic variants affecting statin efficacy, a critical class of cholesterol-lowering drugs.
Purpose of the Study:
- To compare statin-induced gene expression changes in LCLs versus primary B-cells from the same donors.
- To determine if EBV transformation influences the cellular response to statins, particularly concerning cholesterol metabolism and other cellular processes.
Main Methods:
- Primary B-cells and LCLs from the same donors were incubated with simvastatin or a sham buffer for 24 hours.
- Messenger RNA (mRNA) profiles were compared between cell types and conditions using transcriptomic analysis.
- Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to assess the enrichment of MYC and EBNA2 transcription factors.
Main Results:
- Statin-induced regulation of cholesterol metabolism genes showed strong correlation between LCLs and primary B-cells.
- Genes with differential expression between LCLs and B-cells were mainly involved in cell cycle, apoptosis, and alternative splicing.
- MYC and EBNA2 binding signals were enriched at promoters of genes upregulated in LCLs, suggesting their role in altered cellular processes.
Conclusions:
- LCLs are a valid model for studying statin effects on cholesterol metabolism.
- EBV transformation in LCLs may impact the observed drug effects on cell cycle, apoptosis, and alternative splicing, necessitating careful consideration in research design.
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