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Lymphoma

Mantle cell lymphoma: transcriptional regulation by microRNAs

Leukemia volume 24, pages 1335–1342 (2010)Cite this article

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Abstract

Mantle cell lymphoma (MCL) pathogenesis is still partially unexplained. We investigate the importance of microRNA (miRNA) expression as an additional feature that influences MCL pathway deregulation and may be useful for predicting patient outcome. Twenty-three MCL samples, eight cell lines and appropriate controls were screened for their miRNAs and gene expression profiles and DNA copy-number changes. MCL patients exhibit a characteristic signature that includes 117 miRNA (false discovery rate <0.05). Combined analysis of miRNAs and the gene expression profile, paired with bioinformatics target prediction (miRBase and TargetScan), revealed a series of genes and pathways potentially targeted by a small number of miRNAs, including essential pathways for lymphoma survival such as CD40, mitogen-activated protein kinase and NF-κB. Functional validation in MCL cell lines demonstrated NF-κB subunit nuclear translocation to be regulated by the expression of miR-26a. The expression of 12 selected miRNAs was studied by quantitative PCR in an additional series of 54 MCL cases. Univariate analysis identified a single miRNA, miR-20b, whose lack of expression distinguished cases with a survival probability of 56% at 60 months. In summary, using a novel bioinformatics approach, this study identified miRNA changes that contribute to MCL pathogenesis and markers of potential utility in MCL diagnosis and clinical prognostication.

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Acknowledgements

We thank the Spanish National Tumour Bank Network (CNIO), the Hospitals of Gregorio Marañon and La Paz, Madrid, Spain, and Virgen de la Salud, Toledo, for sample retrieval and tumor banking; Santiago Montes-Moreno and Socorro M Rodríguez-Pinilla for reviewing and confirming the diagnosis of the samples; Orlando Domínguez for help with the genomic studies; Maria J Artiga for qPCR procedures and Núria Malats for survival analysis; the CNIO confocal microscopy and flow cytometry units. This study was supported by grants from the Ministerio de Sanidad y Consumo (RETICS, PI051623, PI052800); (FI08/00038) (LDL) and Fundación Mutua Madrileña (LDL), (CP06/00002) (NM); the Ministerio de Ciencia y Tecnología (SAF2005-00221, SAF2008-03871, SAF2007-65957-C02-02), Fundación la Caixa; the National Institute of Bioinformatics (GG-L); Marie-Curie PhD ESRT (MEST-2-CT-2004-6423) (BIF); the Ministerio de Ciencia e Innovación PI08-0440 (JCC), Spain.

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Authors and Affiliations

  1. Lymphoma Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    L Di Lisio, M Sánchez-Beato, C Gómez-Abad, M E Rodríguez, R Villuendas, M A Piris & N Martínez

  2. Bioinformatics Unit, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    G Gómez-López, A Carro, D Rico & D G Pisano

  3. Molecular Cytogenetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    B I Ferreira & J C Cigudosa

  4. Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain

    M Mollejo

  5. Department of Pathology, Hospital Doce de Octubre, Madrid, Spain

    M A Martínez

  6. Department of Pathology, Hospital Gregorio Marañon, Madrid, Spain

    J Menárguez

  7. Department of Immunology, Hospital Gregorio Marañon, Madrid, Spain

    A Díaz-Alderete & J Gil

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  1. L Di Lisio
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Correspondence to M A Piris.

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Di Lisio, L., Gómez-López, G., Sánchez-Beato, M. et al. Mantle cell lymphoma: transcriptional regulation by microRNAs. Leukemia 24, 1335–1342 (2010). https://doi.org/10.1038/leu.2010.91

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