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Annals of Hematology

, Volume 95, Issue 6, pp 881–891 | Cite as

miR-17-92 cluster components analysis in Burkitt lymphoma: overexpression of miR-17 is associated with poor prognosis

  • Marcela Cristina Robaina
  • Roberta Soares Faccion
  • Luciano Mazzoccoli
  • Lidia Maria M. Rezende
  • Eduardo Queiroga
  • Carlos E. Bacchi
  • Andrei Thomas-Tikhonenko
  • Claudete Esteves KlumbEmail author
Original Article

Abstract

Burkitt lymphoma (BL) is an aggressive B cell lymphoma characterized by the reciprocal translocation of the c-Myc gene with immunoglobulin genes. Recently, MYC has been shown to maintain the neoplastic state via the miR-17-92 microRNA cluster that suppresses chromatin regulatory genes and the apoptosis regulator Bim. However, the expression and prognostic impact of miR-17-92 members in pediatric BL (pBL) are unknown. Therefore, we investigated miR-17, miR-19a, miR-19b, miR-20, and miR-92a expression and prognostic impact in a series of 41 pBL samples. In addition, Bim protein expression was evaluated and compared to miR-17, miR-19a, miR-19b, miR-20, and miR-92a levels and patient outcomes. The expression of miR-17-92 members was evaluated by qPCR and Bim protein by immunohistochemistry. Log-rank test was employed to assess prognostic impact. We found that upregulated expression of miR-17 and miR-20a correlates with lack of pro-apoptotic Bim expression. Patients bearing tumors with upregulated miR-17 displayed decreased overall survival (OS), and multivariate analysis revealed that miR-17 was a significant predictor of shortened OS. Using hairpin inhibitors, we showed that inhibition of miR-17 resulted in enhanced Bim expression in a BL cell line overexpressing the miR-17-92 cluster. Our results describe for the first time miR-17, miR-19a, miR-19b, miR-20a, and miR-92a expression profiles in pBL. The prognostic impact of miR-17 should be validated in a larger series, and may provide new therapeutic avenues in the era of anti-miRNA therapy research. Additional functional studies are further required to understand the specific role of miR-17-92 cluster members in BL.

Keywords

Burkitt lymphoma miR-17-92 cluster MYC Bim miR-17 and miR-20a family Prognosis 

Notes

Acknowledgments

We are grateful to all the clinicians who followed the patients included in the study. This work was supported by grants from Instituto Nacional de Ciência e Tecnologia (INCT) para Controle do Câncer: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 573806/2008-0/FAPERJ E26/170.026/2008, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) E-26/110.238/2014—PPSUS, Programa de Oncobiologia/Fundação do Câncer, and FAPERJ E-26/110.375/2014. SWISS-BRIDGE Foundation, sub-project 1B/2014. MCR and RSF had a scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-PDSE) and Ministério da Saúde/INCA, respectively.

Compliance with ethical standards

The study was approved by the institutional ethics committee (registration number 18/09), in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Marcela Cristina Robaina
    • 1
    • 4
  • Roberta Soares Faccion
    • 1
  • Luciano Mazzoccoli
    • 1
  • Lidia Maria M. Rezende
    • 2
  • Eduardo Queiroga
    • 3
  • Carlos E. Bacchi
    • 3
  • Andrei Thomas-Tikhonenko
    • 4
    • 5
  • Claudete Esteves Klumb
    • 1
    • 6
    Email author
  1. 1.Programa de Pesquisa em Hemato-Oncologia MolecularInstituto Nacional de CâncerRio de JaneiroBrazil
  2. 2.Divisão de PatologiaInstituto Nacional de CâncerRio de JaneiroBrazil
  3. 3.Consultoria em PatologiaBotucatuBrazil
  4. 4.Division of Cancer PathobiologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  5. 5.Department of Pathology and Laboratory MedicinePerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  6. 6.Laboratório de Hemato-Oncologia Celular e MolecularRio de JaneiroBrazil

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