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The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity
Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnosti...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458184/ https://www.ncbi.nlm.nih.gov/pubmed/28415684 http://dx.doi.org/10.18632/oncotarget.16049 |
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author | Laneve, Pietro Po, Agnese Favia, Annarita Legnini, Ivano Alfano, Vincenzo Rea, Jessica Carlo, Valerio Di Bevilacqua, Valeria Miele, Evelina Mastronuzzi, Angela Carai, Andrea Locatelli, Franco Bozzoni, Irene Ferretti, Elisabetta Caffarelli, Elisa |
author_facet | Laneve, Pietro Po, Agnese Favia, Annarita Legnini, Ivano Alfano, Vincenzo Rea, Jessica Carlo, Valerio Di Bevilacqua, Valeria Miele, Evelina Mastronuzzi, Angela Carai, Andrea Locatelli, Franco Bozzoni, Irene Ferretti, Elisabetta Caffarelli, Elisa |
author_sort | Laneve, Pietro |
collection | PubMed |
description | Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA-induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p, miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de-repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic expression in the aggressive Group 3 MB cells attenuates their proliferation, migration and invasion. This study unveils the first lncRNA-based ceRNA network in central nervous system tumours and provides a novel molecular circuit underlying the enigmatic Group 4 medulloblastoma. |
format | Online Article Text |
id | pubmed-5458184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54581842017-06-08 The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity Laneve, Pietro Po, Agnese Favia, Annarita Legnini, Ivano Alfano, Vincenzo Rea, Jessica Carlo, Valerio Di Bevilacqua, Valeria Miele, Evelina Mastronuzzi, Angela Carai, Andrea Locatelli, Franco Bozzoni, Irene Ferretti, Elisabetta Caffarelli, Elisa Oncotarget Research Paper Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA-induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p, miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de-repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic expression in the aggressive Group 3 MB cells attenuates their proliferation, migration and invasion. This study unveils the first lncRNA-based ceRNA network in central nervous system tumours and provides a novel molecular circuit underlying the enigmatic Group 4 medulloblastoma. Impact Journals LLC 2017-03-09 /pmc/articles/PMC5458184/ /pubmed/28415684 http://dx.doi.org/10.18632/oncotarget.16049 Text en Copyright: © 2017 Laneve et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Laneve, Pietro Po, Agnese Favia, Annarita Legnini, Ivano Alfano, Vincenzo Rea, Jessica Carlo, Valerio Di Bevilacqua, Valeria Miele, Evelina Mastronuzzi, Angela Carai, Andrea Locatelli, Franco Bozzoni, Irene Ferretti, Elisabetta Caffarelli, Elisa The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity |
title | The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity |
title_full | The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity |
title_fullStr | The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity |
title_full_unstemmed | The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity |
title_short | The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity |
title_sort | long noncoding rna linc-ned125 controls the expression of medulloblastoma driver genes by microrna sponge activity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458184/ https://www.ncbi.nlm.nih.gov/pubmed/28415684 http://dx.doi.org/10.18632/oncotarget.16049 |
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