Overexpression of MicroRNAs from the miR-17-92 Paralog Clusters in AIDS-Related Non-Hodgkins LymphomasReportar como inadecuado




Overexpression of MicroRNAs from the miR-17-92 Paralog Clusters in AIDS-Related Non-Hodgkins Lymphomas - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Individuals infected by HIV are at an increased risk for developing non-Hodgkin-s lymphomas AIDS-NHL. In the highly active antiretroviral therapy HAART era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma PCNSL. However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.

Methodology-Principal Findings

We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt-s lymphoma BL, n = 6, diffuse large B-cell lymphoma DLBCL, n = 8, primary central nervous system lymphoma PCNSL, n = 5, and primary effusion lymphoma PEL, n = 5. We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils n = 4. miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters miR-17, miR-106a, and miR-106b inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis.

Conclusion

Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs.



Autor: Dharma R. Thapa, Xinmin Li, Beth D. Jamieson, Otoniel Martínez-Maza

Fuente: http://plos.srce.hr/



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