TY - JOUR
T1 - The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity
AU - Laneve, Pietro
AU - Po, Agnese
AU - Favia, Annarita
AU - Legnini, Ivano
AU - Alfano, Vincenzo
AU - Rea, Jessica
AU - Di Carlo, Valerio
AU - Bevilacqua, Valeria
AU - Miele, Evelina
AU - Mastronuzzi, Angela
AU - Carai, Andrea
AU - Locatelli, Franco
AU - Bozzoni, Irene
AU - Ferretti, Elisabetta
AU - Caffarelli, Elisa
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Cancer driver genes
KW - Competing endogenous RNAs
KW - Group 4 medulloblastoma
KW - Long noncoding RNAs
KW - MicroRNAs
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U2 - 10.18632/oncotarget.16049
DO - 10.18632/oncotarget.16049
M3 - Article
AN - SCOPUS:85019163554
VL - 8
SP - 31003
EP - 31015
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 19
ER -