Expression of the transcribed ultraconserved region 70 and the related long non-coding RNA AC092652.2-202 has prognostic value in Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukemia (CLL) development and progression is known to be affected by a plethora of external signals. Among the receptors sensitive to such stimuli, toll-like receptor 9 (TLR9) is of interest because treatment with an agonist like CpG-oligodeoxynucleotide (CpG-ODN) impacts in tumor cell viability and immunogenicity through rendering them more sensitive to T cell-mediated cytotoxicity and chemotherapeutic agents in vitro. Long non-coding RNA (lncRNA) expression alterations have been implicated in various neoplasms including CLL, suggesting that they could also be therapeutic targets and/or clinically useful biomarkers. Transcribed Ultraconserved Regions (T-UCRs) are a class of lncRNA comprising a total of 481 different transcripts with an absolute degree of conservation among human, mouse and rat, that it is suggestive of an essential functional relevance in mammals. In the present study we have explored the possible role of T-UCR in the pathogenesis of CLL performing a global screening using microarrays and qRT-PCR in response to CpG-ODN stimulation. We have identified a AC092652.2-202 as the uc.70-related lncRNA which expression levels are related to the response to CpG-ODN and have prognostic significance in CLL. These findings warrant further studies on the functional characterization of this lncRNA in CLL as well of the particular role of uc.70 sequence in its expression regulationFil: Bomben, Riccardo. University of Miami; Estados Unidos. Centro Di Riferimento Oncologico; ItaliaFil: Roisman, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; España. University of Miami; Estados UnidosFil: D'Agaro, Tiziana. Centro Di Riferimento Oncologico; ItaliaFil: Castellano, Giancarlo. Hospital Clínico de Barcelona; EspañaFil: Baumann, Tycho. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; España. Hospital Clínico de Barcelona; EspañaFil: Delgado, Julio. Hospital Clínico de Barcelona; España. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; EspañaFil: López Guillermo, Armando. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; España. Hospital Clínico de Barcelona; EspañaFil: Zucchetto, Antonella. Centro Di Riferimento Oncologico; ItaliaFil: Dal Bo, Michele. Centro Di Riferimento Oncologico; ItaliaFil: Bravin, Vanessa. Centro Di Riferimento Oncologico; ItaliaFil: 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; ArgentinaFil: Vlasova, Anna. Barcelona Institute Of Science And Technology.; EspañaFil: Guigó, Roderic. Barcelona Institute Of Science And Technology.; EspañaFil: Martin Subero, Jose I.. Centro de Investigación Biomédica en Red de Cáncer ; España. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; EspañaFil: Chapaprieta, Vicente. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; EspañaFil: Beekman, Renee. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; España. Centro de Investigación Biomédica en Red de Cáncer ; EspañaFil: Martin García, David. Centro de Investigación Biomédica en Red de Cáncer ; España. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; EspañaFil: Beà, Sílvia. Centro de Investigación Biomédica en Red de Cáncer ; España. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; EspañaFil: Salaverria, Itziar. Centro de Investigación Biomédica en Red de Cáncer ; España. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; EspañaFil: Aymerich, Marta. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; España. Hospital Clínico de Barcelona; EspañaFil: Campo, Elias. Centro de Investigación Biomédica en Red de Cáncer ; España. Hospital Clínico de Barcelona; España. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; EspañaFil: Gattei, Valter. Centro Di Riferimento Oncologico; ItaliaFil: Hernández, Luis. Centro de Investigación Biomédica en Red de Cáncer ; España. Institut d'Investigacions Biomèdiques August Pi i Sunyer. Lymphoid Neoplasm Program; Españ

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; ArgentinaFil: Castellano, Giancarlo. Universidad de Barcelona; EspañaFil: Navarro, Alba. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; EspañaFil: Gonzalez Farre, Blanca. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Universidad de Barcelona; EspañaFil: Pérez Galan, Patricia. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; EspañaFil: Esteve Codina, Anna. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; EspañaFil: Dabad, Marc. Barcelona Institute Of Science And Technology.; España. Universitat Pompeu Fabra; EspañaFil: Heath, Simon. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; EspañaFil: Gut, Marta. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; EspañaFil: Bosio, Mattia. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; EspañaFil: Bellot, Pau. Barcelona Institute Of Science And Technology. Institut Català D'investigació Química.; EspañaFil: Salembier, Philippe. Universidad Politécnica de Catalunya; EspañaFil: Oliveras, Albert. Universidad Politécnica de Catalunya; EspañaFil: 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; ArgentinaFil: Magnano, Andrea Laura. Hospital Clínico de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Horn, Heike. Eberhard Karls Universität Tübingen.; AlemaniaFil: Rosenwald, Andreas. University of Würzburg; AlemaniaFil: Ott, German. Department of Clinical Pathology; AlemaniaFil: Aymerich, Marta. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; EspañaFil: López Guillermo, Armando. Hospital Clínico de Barcelona; EspañaFil: Jares, Pedro. Universidad de Barcelona; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; EspañaFil: Martín Subero, José I.. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; EspañaFil: 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; EspañaFil: Hernández, Luis. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Centro de Investigación Biomédica en Red de Cáncer; Españ