The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity

Pietro Laneve, Agnese Po, Annarita Favia, Ivano Legnini, Vincenzo Alfano, Jessica Rea, Valerio Di Carlo, Valeria Bevilacqua, Evelina Miele, Angela Mastronuzzi, Andrea Carai, Franco Locatelli, Irene Bozzoni, Elisabetta Ferretti, Elisa Caffarelli

Research output: Contribution to journalArticle

Abstract

Long noncoding RNAs (lncRNAs) are major regulators of physiological and diseaserelated gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissuespecificity 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.

Original languageEnglish
Pages (from-to)31003-31015
Number of pages13
JournalOncotarget
Volume8
Issue number19
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Cancer driver genes
  • Competing endogenous RNAs
  • Group 4 medulloblastoma
  • Long noncoding RNAs
  • MicroRNAs

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Laneve, P., Po, A., Favia, A., Legnini, I., Alfano, V., Rea, J., Di Carlo, V., Bevilacqua, V., Miele, E., Mastronuzzi, A., Carai, A., Locatelli, F., Bozzoni, I., Ferretti, E., & Caffarelli, E. (2017). The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity. Oncotarget, 8(19), 31003-31015. https://doi.org/10.18632/oncotarget.16049