Oncotarget

Research Papers:

Primary mediastinal large B-cell lymphoma: transcriptional regulation by miR-92a through FOXP1 targeting

Martha Romero, Guillaume Gapihan, Luis Jaime Castro-Vega, Andrés Acevedo, Li Wang, Zhao Wei Li, Morad El Bouchtaoui, Mélanie Di Benedetto, Philippe Ratajczak, Jean-Paul Feugeas, Catherine Thieblemont, Carlos Saavedra and Anne Janin _

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Oncotarget. 2017; 8:16243-16258. https://doi.org/10.18632/oncotarget.12988

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Abstract

Martha Romero1,2,3,*, Guillaume Gapihan1,2,*, Luis Jaime Castro-Vega4, Andrés Acevedo3, Li Wang1,5, Zhao Wei Li1,5, Morad El Bouchtaoui1 , Mélanie Di Benedetto1, Philippe Ratajczak1,2, Jean-Paul Feugeas1,6, Catherine Thieblemont7, Carlos Saavedra3 and Anne Janin1,2,8

1 Université-Paris-Diderot, Sorbonne-Paris-Cité, Laboratoire de Pathologie, UMR-S-1165, Paris, France

2 INSERM, U1165-Paris, Paris, France

3 Hospital-Universitario-Fundación-Santa-Fe-de-Bogotá, Pathology-Department, Bogotá, Colombia

4 INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France

5 Pôle-Recherches Sino-Français en Science du Vivant Génomique, Molecular-Pathology, Shanghai, China

6 INSERM, U1137, Paris, France

7 AP-HP-Hôpital Saint-Louis, Hemato-oncology-Department –Paris, Paris, France

8 AP-HP-Hôpital Saint-Louis, Pathology-Department–Paris, Paris, France

* These authors have contributed equally to this work

Correspondence to:

Anne Janin, email:

Keywords: primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, miR-17-92 oncogenic cluster, FOXP1, bioinformatics approach

Received: September 30, 2016 Accepted: October 07, 2016 Published: October 28, 2016

Abstract

Background: 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.

Methods: Here 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.

Results: We 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 3’UTR, 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.

Conclusions: We concluded to a post-transcriptional regulation by miR-92a through FOXP1 targeting in PMBL, with a clinico-pathological relevance for better characterisation of PMBL.


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