title: Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools.
abstract: Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.
authors.affiliation: Ministry of Justice, Department of Biology, Council of Forensic Medicine, Istanbul, Turkey, drmuratcanturk@yahoo.com.
authors.forename: Kemal Murat
authors.initials: KM
authors.lastname: Canturk
authors.forename: Muhsin
authors.initials: M
authors.lastname: Ozdemir
authors.forename: Cavit
authors.initials: C
authors.lastname: Can
authors.forename: Setenay
authors.initials: S
authors.lastname: Öner
authors.forename: Ramazan
authors.initials: R
authors.lastname: Emre
authors.forename: Huseyin
authors.initials: H
authors.lastname: Aslan
authors.forename: Oguz
authors.initials: O
authors.lastname: Cilingir
authors.forename: Evrim
authors.initials: E
authors.lastname: Ciftci
authors.forename: Fatih Mehmet
authors.initials: FM
authors.lastname: Celayir
authors.forename: Ozgur
authors.initials: O
authors.lastname: Aldemir
authors.forename: Mustafa
authors.initials: M
authors.lastname: Özen
authors.forename: Sevilhan
authors.initials: S
authors.lastname: Artan
mesh_terms: D019295:Computational Biology / Q000379:methods*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012984:Software; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D035683:MicroRNAs; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6