The Epstein Barr-encoded BART-6-3p microRNA affects regulation of cell growth and immuno response in Burkitt lymphoma

Burkitt lymphoma is an aggressive B-cell lymphoma presenting in three clinical forms: endemic, sporadic and immunodeficiency-associated. More than 90% of endemic Burkitt lymphoma carry latent Epstein-Barr virus, whereas only 20% of sporadic Burkitt lymphoma are associated with Epstein-Barr infection...

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Bibliographic Details
Published in:Infectious agents and cancer 2014-04, Vol.9 (1), p.12-12, Article 12
Main Authors: Ambrosio, Maria Raffaella, Navari, Mohsen, Di Lisio, Lorena, Leon, Eduardo Andres, Onnis, Anna, Gazaneo, Sara, Mundo, Lucia, Ulivieri, Cristina, Gomez, Gonzalo, Lazzi, Stefano, Piris, Miguel Angel, Leoncini, Lorenzo, De Falco, Giulia
Format: Article
Language:English
Subjects:
Burkitt's lymphoma
Care and treatment
Cell growth
Comparative analysis
Epstein-Barr virus
Gene expression
Genetic aspects
Genomes
Health aspects
Hybridization
Immunodeficiency
Infection
Lymphoma
Medical research
MicroRNAs
Pathogenesis
Physiological aspects
Risk factors
Rodents
Studies
Tumorigenesis
Tumors
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Summary:Burkitt lymphoma is an aggressive B-cell lymphoma presenting in three clinical forms: endemic, sporadic and immunodeficiency-associated. More than 90% of endemic Burkitt lymphoma carry latent Epstein-Barr virus, whereas only 20% of sporadic Burkitt lymphoma are associated with Epstein-Barr infection. Although the Epstein-Barr virus is highly related with the endemic form, how and whether the virus participates in its pathogenesis remains to be fully elucidated. In particular, the virus may impair cellular gene expression by its own encoded microRNAs. Using microRNA profiling we compared Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases for both cellular and viral microRNAs. The array results were validated by qRT-PCR, and potential targets of viral microRNAs were then searched by bioinformatic predictions, and classified in functional categories, according to the Gene Ontology. Our findings were validated by in vitro functional studies and by immunohistochemistry on a larger series of cases. We showed that a few cellular microRNAs are differentially expressed between Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases, and identified a subset of viral microRNAs expressed in Epstein-Barr-positive Burkitt lymphomas. Of these, we characterized the effects of viral BART6-3p on regulation of cellular genes. In particular, we analyzed the IL-6 receptor genes (IL-6Rα and IL-6ST), PTEN and WT1 expression for their possible relevance to Burkitt lymphoma. By means of immunohistochemistry, we observed a down-regulation of the IL-6 receptor and PTEN specifically in Epstein-Barr-positive Burkitt lymphoma cases, which may result in the impairment of key cellular pathways and may contribute to malignant transformation. On the contrary, no differences were observed between Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases for WT1 expression. Our preliminary results point at an active role for the Epstein-Barr virus in Burkitt lymphomagenesis and suggest new possible mechanisms used by the virus in determining dysregulation of the host cell physiology.
ISSN:1750-9378
1750-9378
DOI:10.1186/1750-9378-9-12