Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer

Abstract

// Luca Falzone 1 , Saverio Candido 1 , Rossella Salemi 1 , Maria S. Basile 1 , Aurora Scalisi 2 , James A. McCubrey 3 , Francesco Torino 4 , Salvatore S. Signorelli 5 , Maurizio Montella 6 , Massimo Libra 1 1 Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of Catania, Catania, Italy 2 Oncological Pathology Unit, ASP, Catania, Italy 3 Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA 4 Department of Systems Medicine, Chair of Medical Oncology, Tor Vergata University of Rome, Rome, Italy 5 Department of Clinical and Experimental Medicine, University of Catania, Medical Angiology Unit, Garibaldi Hospital, Catania, Italy 6 Unit of Epidemiology, ‘Fondazione G. Pascale’, Istituto Nazionale Tumori, Naples, Italy Correspondence to: Massimo Libra, email: mlibra@unict.it Keywords: bladder cancer, bioinformatics, miRNAs, epithelial-mesenchymal transition, NGAL/MMP-9 Received: July 06, 2016      Accepted: August 25, 2016      Published: September 01, 2016 ABSTRACT Bladder cancer is one of the leading cancer of the urinary tract. It is often diagnosed at advanced stage of the disease. To date, no specific and effective early detection biomarkers are available. Cancer development and progression are associated with the involvement of both epithelial-mesenchymal transition (EMT) and tumor microenvironment of which NGAL/MMP-9 complex represents the main player in bladder cancer. It is known that change in microRNAs (miRNAs) expression may result in gene modulation. Therefore, the identification of specific miRNAs associated with EMT pathway and NGAL/MMP-9 complex may be useful to detect the development of bladder cancer at early stages. On this ground, the expression levels of miRNAs in public available datasets of bladder cancer containing data of non-coding RNA profiling was evaluated. This analysis revealed a group of 16 miRNAs differentially expressed between bladder cancer patients and related healthy controls. By miRNA prediction tool (mirDIP), the relationship between the identified miRNAs and the EMT genes was established. Using the DIANA-mirPath (v.2) software, miRNAs, able to modulate the expression of NGAL and MMP-9 genes, were recognized. The results of this study provide evidence that the downregulated hsa-miR-145-5p and hsa-miR-214-3p may modulate the expression of both EMT and NGAL/MMP-9 pathways. Therefore, further validation analyses may confirm the usefulness of these selected miRNAs for predicting the development of bladder cancer at the early stage of the disease.