Barbagallo Davide, Condorelli Angelo, Ragusa Marco, Salito Loredana, Sammito Mariangela, Banelli Barbara, Caltabiano Rosario, Barbagallo Giuseppe, Zappalà Agata, Battaglia Rosalia, Cirnigliaro Matilde, Lanzafame Salvatore, Vasquez Enrico, Parenti Rosalba, Cicirata Federico, Di Pietro Cinzia, Romani Massimo, Purrello Michele
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.
UOS Epigenetica dei Tumori, IRCCS A.O.U. San Martino-IST, Genova, Italy, EU.
Oncotarget. 2016 Jan 26;7(4):4746-59. doi: 10.18632/oncotarget.6621.
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.
MiR-671-5p由位于7q36.1的一个基因编码,该区域在多形性胶质母细胞瘤(GBM)中扩增,GBM是最恶性的脑癌。为了研究GBM中miR-671-5p的表达是否改变,我们分析了45例GBM患者的活检样本以及5种GBM细胞系。我们的数据显示,miR-671-5p在活检样本和细胞系中均显著过表达。通过利用特定的miRNA模拟物和抑制剂,我们证明miR-671-5p的过表达显著增加了GBM细胞的迁移能力,并在较小程度上提高了其增殖率。通过计算机模拟和体外实验相结合的方法,我们确定CDR1-AS、CDR1、VSNL1是GBM中miR-671-5p的下游靶点。这些基因的表达在GBM活检样本和细胞系中均显著降低,且与miR-671-5p的表达呈负相关。基于我们的数据,我们提出miR-671-5p / CDR1-AS / CDR1 / VSNL1轴在GBM细胞中功能发生改变,并参与了其生物病理特征的改变。