Screening and functional analysis of differentially expressed genes in EBV-transformed lymphoblasts
Open accessAbstract
Background: Epstain-Barr virus (EBV) can transform human B lymphocytes making them immortalized and inducing tumorigenic ability in vitro, but the molecular mechanisms remain unclear. The aim of the present study is to detect and analyze differentially expressed genes in two types of host cells, normal human lymphocytes and coupled EBV-transformed lymphoblasts in vitro using gene chips, and to screen the key regulatory genes of lymphocyte transformation induced by EB virus. Methods: Fresh peripheral blood samples from seven healthy donors were collected. EBV was used to transform lymphocytes in vitro. Total RNA was extracted from 7 cases of the normal lymphocytes and transformed lymphoblasts respectively, marked with dihydroxyfluorane after reverse transcription, then hybridized with 4 × 44 K Agilent human whole genome microarray. LIMMA, String, Cytoscape and other softwares were used to screen and analyze differentially expressed genes. Real-time PCR was applied to verify the result of gene expression microarrays. Results: There were 1745 differentially expressed genes that had been screened, including 917 up-regulated genes and 828 down-regulated genes. According to the results of Generank, String and Cytoscape analyses, 38 genes may be key controlled genes related to EBV-transformed lymphocytes, including 22 up-regulated genes(PLK1, E2F1, AURKB, CDK2, PLCG2, CD80, PIK3R3, CDC20, CDC6, AURKA, CENPA, BUB1B, NUP37, MAD2L1, BIRC5, CDC25A, CCNB1, RPA3, HJURP, KIF2C, CDK1, CDCA8) and 16 down-regulated genes(FYN, CD3D, CD4, CD3G, ZAP70, FOS, HCK, CD247, PRKCQ, ITK, LCP2, CXCL1, CD8A, ITGB5, VAV3, CXCR4), which primarily control biological processes such as cell cycle, mitosis, cytokine-cytokine pathway, immunity response and so on. Conclusions: Human lymphocyte transformation induced by EB virus is a complicated process, involving multiple-genes and –pathways in virus-host interactions. Global gene expression profile analysis showed that EBV may transform human B lymphocytes by promoting cell cycle and mitosis, inhibiting cell apoptosis, hindering host immune function and secretion of cytokines.
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PLCγ2 was shown to be upregulated in EBV-transformed lymphoblasts.
“While PLCγ2 signaling is apparently blocked during EBV infection, it was also conversely shown to be upregulated in EBV-transformed lymphoblasts (141).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [141]
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- Authors
- Dai, Y., Tang, Y., He, F., Zhang, Y., Cheng, A., Gan, R., & Wu, Y.
- Affiliations
- University of South China (CN)
- Shanghai Center For Bioinformation Technology (CN)
- Corresponding author
- Gan, Runliang
- Wu, Yimou
- Venue
- Virology Journal
- Published
- 2012-03-30
- Volume
- 9
- Issue
- 1
- Pages
- 77-77
- ISSN
- 1743-422X (ISSN-L)
- PMC
- PMC3433351
- OpenAlex
- W1974317120
- Cited by
- 40
- References
- 29
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 4 · 2013: 8
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Virology Journal (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81072198)
- Construct Program of the Key Discipline in Hunan Province (2011–76)
- Topics
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- Epstein-Barr virus, B lymphocyte transformation, differentially expressed genes, gene expression profiling, cell cycle genes, mitosis, immune response, host-virus interaction, cell proliferation, apoptosis, cell adhesion, cell motility, cell migration, cell cycle checkpoint genes, cell cycle regulatory genes
- MeSH terms
- Cell Line, Transformed, Cell Transformation, Viral, Herpesvirus 4, Human, Gene Expression Regulation, Humans, Lymphocyte Activation, Lymphocytes, Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling
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