Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme
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Davide Barbagallo1,¶, Angelo Condorelli1,¶, Marco Ragusa1,¶, Loredana Salito1, Mariangela Sammito1, Barbara Banelli2, Rosario Caltabiano3, Giuseppe Barbagallo3, Agata Zappalà4, Rosalia Battaglia1, Matilde Cirnigliaro1, Salvatore Lanzafame3, Enrico Vasquez3, Rosalba Parenti4, Federico Cicirata4, Cinzia Di Pietro1,*, Massimo Romani2,*, Michele Purrello1,*
1Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biologia e Genetica G Sichel, Unità di BioMedicina Molecolare, Genomica e dei Sistemi Complessi, Università di Catania, Catania, Italy, EU
2UOS Epigenetica dei Tumori, IRCCS A.O.U. San Martino-IST, Genova, Italy, EU
3Dipartimento di Scienze Mediche, Chirurgiche e Tecnologie Avanzate G.F. Ingrassia, Università di Catania, Catania, Italy, EU
4Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Fisiologia, Università di Catania, Catania, Italy, EU
¶These authors contributed equally to this work
*Senior Corresponding Authors
Michele Purrello, e-mail: [email protected]
Keywords: glioblastoma multiforme (GBM), non coding RNAs (ncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), cell networks
Received: May 25, 2015 Accepted: November 14, 2015 Published: December 15, 2015
MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.
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