Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas

Long non‐coding RNA s (lncRNA s) comprise a family of non‐coding transcripts that are emerging as relevant gene expression regulators of different processes, including tumour development. To determine the possible contribution of lncRNA to the pathogenesis of follicular lymphoma (FL ) we performed RNA ‐sequencing at high depth sequencing in primary FL samples ranging from grade 1‐3A to aggressive grade 3B variants using unpurified (n = 16) and purified (n = 12) tumour cell suspensions from nodal samples. FL grade 3B had a significantly higher number of differentially expressed lncRNA s (dif‐lncRNA s) with potential target coding genes related to cell cycle regulation. Nine out of the 18 selected dif‐lncRNA s were validated by quantitative real time polymerase chain reaction in an independent series (n = 43) of FL . RP 4‐694A7.2 was identified as the top deregulated lncRNA potentially involved in cell proliferation. RP 4‐694A7.2 silencing in the WSU ‐FSCCL FL cell line reduced cell proliferation due to a block in the G1/S phase. The relationship between RP 4‐694A7.2 and proliferation was confirmed in primary samples as its expression levels positively related to the Ki‐67 proliferation index. In summary, lncRNA s are differentially expressed across the clinico‐biological spectrum of FL and a subset of them, related to cell cycle, may participate in cell proliferation regulation in these tumours. Fil: Roisman, Alejandro. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Castellano, Giancarlo. Universidad de Barcelona; España Fil: Navarro, Alba. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Gonzalez Farre, Blanca. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Universidad de Barcelona; España Fil: Pérez Galan, Patricia. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Esteve Codina, Anna. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; España Fil: Dabad, Marc. Barcelona Institute Of Science And Technology.; España. Universitat Pompeu Fabra; España Fil: Heath, Simon. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; España Fil: Gut, Marta. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; España Fil: Bosio, Mattia. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España Fil: Bellot, Pau. Barcelona Institute Of Science And Technology. Institut Català D'investigació Química.; España Fil: Salembier, Philippe. Universidad Politécnica de Catalunya; España Fil: Oliveras, Albert. Universidad Politécnica de Catalunya; España Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Magnano, Andrea Laura. Hospital Clínico de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Horn, Heike. Eberhard Karls Universität Tübingen.; Alemania Fil: Rosenwald, Andreas. University of Würzburg; Alemania Fil: Ott, German. Department of Clinical Pathology; Alemania Fil: Aymerich, Marta. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: López Guillermo, Armando. Hospital Clínico de Barcelona; España Fil: Jares, Pedro. Universidad de Barcelona; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Martín Subero, José I.. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Campo, Elías. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Hospital Clínico de Barcelona; España Fil: Hernández, Luis. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Centro de Investigación Biomédica en Red de Cáncer; España