Abstract
BackgroundPrimary mediastinal large B-cell lymphoma (PMBL) shares pathological features with diffuse large B-cell lymphoma (DLBCL), and molecular features with classical Hodgkin lymphoma (cHL). The miR-17∼92 oncogenic cluster, located at chromosome 13q31, is a region that is amplified in DLBCL.MethodsHere we compared the expression of each member of the miR-17∼92 oncogenic cluster in samples from 40 PMBL patients versus 20 DLBCL and 20 cHL patients, and studied the target genes linked to deregulated miRNA in PMBL.ResultsWe found a higher level of miR-92a in PMBL than in DLBCL, but not in cHL. A combination of in silico prediction and transcriptomic analyses enabled us to identify FOXP1 as a main miR-92a target gene in PMBL, a result so far not established. This was confirmed by 3UTR, and RNA and protein expressions in transduced cell lines. In vivo studies using the transduced cell lines in mice enabled us to demonstrate a tumor suppressor effect of miR-92a and an oncogenic effect of FOXP1.A higher expression of miR-92a and the down-regulation of FOXP1 mRNA and protein expression were also found in human samples of PMBL, while miR-92a expression was low and FOXP1 was high in DLBCL.ConclusionsWe concluded to a post-transcriptional regulation by miR-92a through FOXP1 targeting in PMBL, with a clinico-pathological relevance for better characterisation of PMBL.
Highlights
Primary mediastinal large B-cell lymphoma (PMBL), which represents 2% to 4% of all non-Hodgkin lymphoma, has been recognized as a separate entity with clinicopathological and molecular characteristics
We found a higher level of miR-92a in PMBL than in diffuse large B-cell lymphoma (DLBCL), but not in classical Hodgkin lymphoma (cHL)
A higher expression of miR-92a and the down-regulation of FOXP1 mRNA and protein expression were found in human samples of PMBL, while miR-92a expression was low and FOXP1 was high in DLBCL
Summary
Primary mediastinal large B-cell lymphoma (PMBL), which represents 2% to 4% of all non-Hodgkin lymphoma, has been recognized as a separate entity with clinicopathological and molecular characteristics. It shares pathological features with diffuse large B-cell lymphoma (DLBCL), and molecular features and better prognosis with the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL) [1]. FOX genes are deregulated in HL [12], and FOXP1 is up-regulated in DLBCLs bearing the chromosomal aberrations trisomy 3 [13], t (3;14) (p13;q32) [14, 15]. Primary mediastinal large B-cell lymphoma (PMBL) shares pathological features with diffuse large B-cell lymphoma (DLBCL), and molecular features with classical Hodgkin lymphoma (cHL). The miR-17~92 oncogenic cluster, located at chromosome 13q31, is a region that is amplified in DLBCL
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