title: Mantle cell lymphoma: transcriptional regulation by microRNAs.
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-kappaB. Functional validation in MCL cell lines demonstrated NF-kappaB 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.
authors.affiliation: Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Di Lisio
authors.forename: G
authors.initials: G
authors.lastname: Gómez-López
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-Beato
authors.forename: C
authors.initials: C
authors.lastname: Gómez-Abad
authors.forename: M E
authors.initials: ME
authors.lastname: Rodríguez
authors.forename: R
authors.initials: R
authors.lastname: Villuendas
authors.forename: B I
authors.initials: BI
authors.lastname: Ferreira
authors.forename: A
authors.initials: A
authors.lastname: Carro
authors.forename: D
authors.initials: D
authors.lastname: Rico
authors.forename: M
authors.initials: M
authors.lastname: Mollejo
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez
authors.forename: J
authors.initials: J
authors.lastname: Menárguez
authors.forename: A
authors.initials: A
authors.lastname: Díaz-Alderete
authors.forename: J
authors.initials: J
authors.lastname: Gil
authors.forename: J C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: D G
authors.initials: DG
authors.lastname: Pisano
authors.forename: M A
authors.initials: MA
authors.lastname: Piris
authors.forename: N
authors.initials: N
authors.lastname: Martínez
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger