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

J Invest Dermatol. 2015 Jun;135(6):1659-1667. doi: 10.1038/jid.2015.27. Epub 2015 Jan 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multigene Family*
  • Multivariate Analysis
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Proportional Hazards Models
  • RNA, Long Noncoding
  • RNA, Messenger / metabolism
  • Skin / metabolism
  • Skin / pathology
  • Skin Neoplasms / genetics*

Substances

  • Antigens, CD20
  • MIR17HG, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • PTEN Phosphohydrolase
  • PTEN protein, human