Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer
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Luca Falzone1, Saverio Candido1, Rossella Salemi1, Maria S. Basile1, Aurora Scalisi2, James A. McCubrey3, Francesco Torino4, Salvatore S. Signorelli5, Maurizio Montella6, Massimo Libra1
1Department 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
2Oncological Pathology Unit, ASP, Catania, Italy
3Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA
4Department of Systems Medicine, Chair of Medical Oncology, Tor Vergata University of Rome, Rome, Italy
5Department of Clinical and Experimental Medicine, University of Catania, Medical Angiology Unit, Garibaldi Hospital, Catania, Italy
6Unit of Epidemiology, ‘Fondazione G. Pascale’, Istituto Nazionale Tumori, Naples, Italy
Massimo Libra, email: [email protected]
Keywords: bladder cancer, bioinformatics, miRNAs, epithelial-mesenchymal transition, NGAL/MMP-9
Received: July 06, 2016 Accepted: August 25, 2016 Published: September 01, 2016
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.
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