The High Expression of the microRNA 17-92 Cluster and its Paralogs, and the Downregulation of the Target Gene PTEN, Is Associated with Primary Cutaneous B-Cell Lymphoma Progression.

Date publication

juin 2015

Journal

The Journal of investigative dermatology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FEUGEAS Jean-Paul

Tous les auteurs :
Battistella M, Romero M, Castro-Vega LJ, Gapihan G, Bouhidel F, Bagot M, Feugeas JP, Janin A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/25634356

Résumé

The oncogenic microRNA (miR) 17-92 cluster has a causative role in the lymphomagenesis of nodal B-cell lymphomas, by activating proliferation and inhibiting apoptosis. Here we analyzed primary cutaneous B-cell lymphomas for the miR-17-92 cluster and its paralogs miR-106a-363 and miR-106b-25. In 22 primary cutaneous diffuse large B-cell lymphomas, leg type (PCLBCL-LT) compared with 22 primary cutaneous follicle center lymphomas (PCFCLs), we found that miR-20a and miR-106a were overexpressed. Multivariate Cox analysis showed that higher miR-20a and miR-20b expression levels were associated with shorter disease-free and overall survival, independently from histological type. Gene expression profiling also showed a downregulation of 8 candidate target genes of miR-20a, miR-20b, and miR-106a in PCLBCL-LT compared with PCFCL. Among the candidate target genes, PTEN, NCOA3, and CAPRIN2 were confirmed to be underexpressed in PCLBCL-LT using quantitative reverse transcriptase-PCR on CD20-positive laser-microdissected tumor cells. In multivariate Cox analysis, lower PTEN mRNA expression level was associated with shorter disease-free survival (DFS), independently from the histological type. Altogether, this molecular and bioinformatic study of 44 patient skin biopsy samples showed that the oncogenic miR-17-92 cluster and its paralogs were involved in cutaneous B-cell lymphoma progression, and that the downregulation of the target gene PTEN was associated with shorter DFS.

Mots clés

Adult, Aged, Aged, 80 and over, Antigens, CD20, metabolism, Apoptosis, Biopsy, Computational Biology, Disease Progression, Disease-Free Survival, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Lymphoma, Large B-Cell, Diffuse, genetics, Male, MicroRNAs, genetics, Middle Aged, Multigene Family, Multivariate Analysis, PTEN Phosphohydrolase, genetics, Proportional Hazards Models, RNA, Messenger, metabolism, Skin, metabolism, Skin Neoplasms, genetics

Référence

J. Invest. Dermatol.. 2015 Jun;135(6):1659-1667