The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells.

dc.contributor.author

Forte, Eleonora

dc.contributor.author

Salinas, Raul E

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Chang, Christina

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Zhou, Ting

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Linnstaedt, Sarah D

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Gottwein, Eva

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Jacobs, Cassandra

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Jima, Dereje

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Li, Qi-Jing

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Dave, Sandeep S

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Luftig, Micah A

dc.date.accessioned

2022-03-28T20:44:43Z

dc.date.available

2022-03-28T20:44:43Z

dc.date.issued

2012-06

dc.date.updated

2022-03-28T20:44:42Z

dc.description.abstract

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.

dc.identifier

JVI.07056-11

dc.identifier.issn

0022-538X

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1098-5514

dc.identifier.uri

https://hdl.handle.net/10161/24738

dc.language

eng

dc.publisher

American Society for Microbiology

dc.relation.ispartof

Journal of virology

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10.1128/jvi.07056-11

dc.subject

B-Lymphocytes

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Cell Line, Tumor

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Humans

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Herpesvirus 4, Human

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Epstein-Barr Virus Infections

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NF-kappa B

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Viral Matrix Proteins

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MicroRNAs

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Cell Proliferation

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Up-Regulation

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Tumor Suppressor Protein p53

dc.title

The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells.

dc.type

Journal article

duke.contributor.orcid

Salinas, Raul E|0000-0001-9011-683X

duke.contributor.orcid

Li, Qi-Jing|0000-0002-0542-9784

duke.contributor.orcid

Luftig, Micah A|0000-0002-2964-1907

pubs.begin-page

6889

pubs.end-page

6898

pubs.issue

12

pubs.organisational-group

Duke

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School of Medicine

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Staff

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Basic Science Departments

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Institutes and Centers

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Biochemistry

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Immunology

pubs.organisational-group

Molecular Genetics and Microbiology

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Duke Cancer Institute

pubs.publication-status

Published

pubs.volume

86

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