The Epstein-Barr Virus (EBV)-Induced Tumor Suppressor MicroRNA MiR-34a Is Growth Promoting in EBV-Infected B Cells
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Epstein-Barr virus (EBV) infection of primary human B cells drives their indefinite proliferation into lymphoblastoid cell lines (LCLs). B cell immortalization depends on expression of viral latency genes, as well as the regulation of host genes. Given the important role of microRNAs (miRNAs) in regulating fundamental cellular processes, in this study, we assayed changes in host miRNA expression during primary B cell infection by EBV. We observed and validated dynamic changes in several miRNAs from early proliferation through immortalization; oncogenic miRNAs were induced, and tumor suppressor miRNAs were largely repressed. However, one miRNA described as a p53-targeted tumor suppressor, miR-34a, was strongly induced by EBV infection and expressed in many EBV and Kaposi's sarcoma-associated herpesvirus (KSHV)-infected lymphoma cell lines. EBV latent membrane protein 1 (LMP1) was sufficient to induce miR-34a requiring downstream NF-κB activation but independent of functional p53. Furthermore, overexpression of miR-34a was not toxic in several B lymphoma cell lines, and inhibition of miR-34a impaired the growth of EBV-transformed cells. This study identifies a progrowth role for a tumor-suppressive miRNA in oncogenic-virus-mediated transformation, highlighting the importance of studying miRNA function in different cellular contexts.
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p53-independent induction of mir-34a by EBV seems necessary for transformation of B lymphocytes.
“For example, p53-independent induction of mir-34a by Epstein-Barr virus (EBV) seems to be necessary for the transformation of B lymphocytes55.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [55]
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- Authors
- Forte, E., Salinas, R. E., Chang, C., Zhou, T., Linnstaedt, S. D., Gottwein, E., Jacobs, C., Jima, D., Li, Q.-J., Dave, S. S., & Luftig, M. A.
- Affiliations
- Duke University (US)
- Duke Medical Center (US)
- Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, USA
- ORCID
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2012-06-15
- Volume
- 86
- Issue
- 12
- Pages
- 6889-6898
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC3393554
- OpenAlex
- W2110752409
- Cited by
- 97
- References
- 50
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 10 · 2014: 7 · 2013: 17 · 2012: 5
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alexander and Margaret Stewart Trust
- University of Pennsylvania
- National Institutes of Health
- National Cancer Institute (K99CA137860, R01CA140337)
- National Institute of Allergy and Infectious Diseases (P30AI045008, T32AI007392)
- Duke Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- Epstein-Barr virus, miR-34a, tumor suppressor microRNA, B cell immortalization, lymphoblastoid cell lines, latent membrane protein 1, NF-κB activation, p53, oncogenic transformation, Kaposi's sarcoma-associated herpesvirus, B cell proliferation, host-virus interaction
- MeSH terms
- B-Lymphocytes, Herpesvirus 4, Human, Humans, Viral Matrix Proteins, Up-Regulation, Tumor Suppressor Protein p53, NF-kappa B, Epstein-Barr Virus Infections, MicroRNAs, Cell Line, Tumor, Cell Proliferation
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