title: Identification of linc-NeD125, a novel long non coding RNA that hosts miR-125b-1 and negatively controls proliferation of human neuroblastoma cells.
abstract: The human genome contains some thousands of long non coding RNAs (lncRNAs). Many of these transcripts are presently considered crucial regulators of gene expression and functionally implicated in developmental processes in Eukaryotes. Notably, despite a huge number of lncRNAs are expressed in the Central Nervous System (CNS), only a few of them have been characterized in terms of molecular structure, gene expression regulation and function. In the present study, we identify linc-NeD125 as a novel cytoplasmic, neuronal-induced long intergenic non coding RNA (lincRNA). Linc-NeD125 represents the host gene for miR-125b-1, a microRNA with an established role as negative regulator of human neuroblastoma cell proliferation. Here, we demonstrate that these two overlapping non coding RNAs are coordinately induced during in vitro neuronal differentiation, and that their expression is regulated by different mechanisms. While the production of miR-125b-1 relies on transcriptional regulation, linc-NeD125 is controlled at the post-transcriptional level, through modulation of its stability. We also demonstrate that linc-NeD125 functions independently of the hosted microRNA, by reducing cell proliferation and activating the antiapoptotic factor BCL-2.
authors.affiliation: a Department of Biology and Biotechnology C. Darwin ; Sapienza University of Rome ; Rome , Italy.|f Present addresses Valeria Bevilacqua: Virology Program, INGM - Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi," Milan, Italy; Ubaldo Gioia: IFOM; the FIRC Institute of Molecular Oncology; Milan, Italy; Valerio Di Carlo: Center for Genomic Regulation and UPF ; Barcelona , Spain.|g These authors equally contributed to this work.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bevilacqua
authors.affiliation: a Department of Biology and Biotechnology C. Darwin ; Sapienza University of Rome ; Rome , Italy.|f Present addresses Valeria Bevilacqua: Virology Program, INGM - Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi," Milan, Italy; Ubaldo Gioia: IFOM; the FIRC Institute of Molecular Oncology; Milan, Italy; Valerio Di Carlo: Center for Genomic Regulation and UPF ; Barcelona , Spain.|g These authors equally contributed to this work.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Gioia
authors.affiliation: a Department of Biology and Biotechnology C. Darwin ; Sapienza University of Rome ; Rome , Italy.|f Present addresses Valeria Bevilacqua: Virology Program, INGM - Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi," Milan, Italy; Ubaldo Gioia: IFOM; the FIRC Institute of Molecular Oncology; Milan, Italy; Valerio Di Carlo: Center for Genomic Regulation and UPF ; Barcelona , Spain.
authors.forename: Valerio
authors.initials: V
authors.lastname: Di Carlo
authors.affiliation: a Department of Biology and Biotechnology C. Darwin ; Sapienza University of Rome ; Rome , Italy.
authors.forename: Anna F
authors.initials: AF
authors.lastname: Tortorelli
authors.affiliation: b Institute for Computing Applications "Mauro Picone," National Research Council ; Rome , Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Colombo
authors.affiliation: a Department of Biology and Biotechnology C. Darwin ; Sapienza University of Rome ; Rome , Italy.|c Institute of Molecular Biology and Pathology, National Research Council, Sapienza University of Rome ; Rome , Italy.|d Institute Pasteur Fondazione Cenci-Bolognetti, Sapienza University of Rome ; Rome , Italy.|e Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia ; Rome , Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bozzoni
authors.affiliation: e Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia ; Rome , Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Laneve
authors.affiliation: c Institute of Molecular Biology and Pathology, National Research Council, Sapienza University of Rome ; Rome , Italy.|e Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia ; Rome , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Caffarelli
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010802:Phylogeny; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C000611467:NeD125 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: apoptosis; cell proliferation; long non coding RNA; miR-125; microRNA; neuroblastoma; neuronal differentiation; post-transcriptional regulation; transcriptional regulation