Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme

Abstract

// Davide Barbagallo 1, ¶ , Angelo Condorelli 1, ¶ , Marco Ragusa 1, ¶ , Loredana Salito 1 , Mariangela Sammito 1 , Barbara Banelli 2 , Rosario Caltabiano 3 , Giuseppe Barbagallo 3 , Agata Zappalà 4 , Rosalia Battaglia 1 , Matilde Cirnigliaro 1 , Salvatore Lanzafame 3 , Enrico Vasquez 3 , Rosalba Parenti 4 , Federico Cicirata 4 , Cinzia Di Pietro 1, * , Massimo Romani 2, * , Michele Purrello 1, * 1 Dipartimento 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 2 UOS Epigenetica dei Tumori, IRCCS A.O.U. San Martino-IST, Genova, Italy, EU 3 Dipartimento di Scienze Mediche, Chirurgiche e Tecnologie Avanzate G.F. Ingrassia , Università di Catania, Catania, Italy, EU 4 Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Fisiologia, Università di Catania, Catania, Italy, EU ¶ These authors contributed equally to this work * Senior Corresponding Authors Correspondence to: Michele Purrello, e-mail: purrello@unict.it 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 ABSTRACT 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.