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

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.
Type de document :
Article dans une revue
Oncotarget, Impact journals, 2016, 〈10.18632/oncotarget.12988〉
Liste complète des métadonnées

Littérature citée [52 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01404979
Contributeur : Philippe Ratajczak <>
Soumis le : mardi 29 novembre 2016 - 14:00:31
Dernière modification le : samedi 22 septembre 2018 - 01:16:45
Document(s) archivé(s) le : lundi 27 mars 2017 - 06:46:37

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

Collections

Citation

Martha Romero, Guillaume Gapihan, Luis Jaime Castro-Vega, Andrés Acevedo, Li Wang, et al.. Primary mediastinal large B-cell lymphoma: transcriptional regulation by miR-92a through FOXP1 targeting. Oncotarget, Impact journals, 2016, 〈10.18632/oncotarget.12988〉. 〈inserm-01404979〉

Partager

Métriques

Consultations de la notice

97