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MicroRNA-124 links p53 to the NF-κB pathway in B-cell lymphomas.
- Source :
-
Leukemia (08876924) . Sep2015, Vol. 29 Issue 9, p1868-1874. 7p. 1 Diagram, 4 Graphs. - Publication Year :
- 2015
-
Abstract
- The contribution of microRNAs to lymphoma biology is not fully understood. In particular, it remains untested whether microRNA dysregulation could contribute to the emergence of the aggressive subset of B-cell lymphomas that coexpress MYC and BCL2. Here, we identify microRNA-124 (miR-124) as a negative regulator of MYC and BCL2 expression in B-cell lymphomas. Concordantly, stable or transient ectopic expression of miR-124 suppressed cell proliferation and survival, whereas genetic inhibition of this miRNA enhanced the fitness of these tumors. Mechanistically, the activities of miR-124 towards MYC and BCL2 intersect with both oncogenic and tumor-suppressive pathways. In respect to the former, we show that miR-124 directly targets nuclear factor-κB (NF-κB) p65, and using genetic approaches, we demonstrate that this interaction accounts for the miR-124-mediated suppression of MYC and BCL2. We also characterized miR-124 promoter region and identified a functional p53 binding site. In agreement with this finding, endogenous or ectopic expression of wild-type, but not mutant, p53 increased miR-124 levels and suppressed p65, MYC and BCL2. Our data unveil an miRNA-dependent regulatory circuitry that links p53 to the NF-κB pathway, which when disrupted in B-cell lymphoma may be associated with aberrant coexpression of MYC and BCL2 and poor prognosis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 29
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 109207316
- Full Text :
- https://doi.org/10.1038/leu.2015.101