Deregulated expression of the imprinted DLK1-DIO3 region in Glioblastoma Stem-like Cells: tumor suppressor role of lncRNA MEG3

Mariachiara Buccarelli, Valentina Lulli, Alessandro Giuliani, Michele Signore, Maurizio Martini, Quintino Giorgio D'Alessandris, Stefano Giannetti, Agnese Novelli, Ramona Ilari, Giorgio Giurato, Alessandra Boe, Giorgia Castellani, Serena Spartano, Giuseppe Marangi, Mauro Biffoni, Maurizio Genuardi, Roberto Pallini, Giovanna Marziali, Lucia Ricci-Vitiani*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

9 Citazioni (Scopus)


Background: Glioblastoma (GBM) stem-like cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted DLK-DIO3 region on chromosome 14q32 in GBM pathogenesis. Methods: RT-PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression and Reverse-Phase protein Array profiles were used to investigate the tumor suppressor function of MEG3. Results: Loss of expression of genes and non-coding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared to normal brain. This down-regulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 lncRNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration and colony formation and decreases in vivo tumor growth reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and Epithelial to Mesenchymal Transition (EMT). Conclusions: In GBM, MEG3 acts as a tumor-suppressor mainly regulating cell adhesion, EMT and cell proliferation, thus providing a potential candidate for novel GBM therapies.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Stato di pubblicazionePubblicato - 2020


  • Cancer stem cells
  • Glioblastoma
  • MEG3 lncRNA
  • chromosome 14q32


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