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Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools

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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.

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Acknowledgments

This research was supported by the Eskisehir Osmangazi University Research Fund with Grant no. 200811031. We are also thankful to Ece TURKMEN, the Product Manager at SEM Laboratuar Cihazlari Paz. San. Tic. A. S, (Istanbul-Turkey), who provided facilities to carry out this study.

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Authors and Affiliations

  1. Ministry of Justice, Department of Biology, Council of Forensic Medicine, Istanbul, Turkey

    Kemal Murat Canturk & Ramazan Emre

  2. Department of Medical Genetics, Eskisehir Osmangazi University, Eskisehir, Turkey

    Kemal Murat Canturk, Muhsin Ozdemir, Huseyin Aslan, Oguz Cilingir & Sevilhan Artan

  3. Department of Urology, Eskisehir Osmangazi University, Eskisehir, Turkey

    Cavit Can

  4. Department of Biostatistics, Eskisehir Osmangazi University, Eskisehir, Turkey

    Setenay Öner

  5. Faculty Department of Pathology, Eskisehir Osmangazi University, Eskisehir, Turkey

    Evrim Ciftci

  6. Department of Medical Genetics, Bursa SevketYılmaz Government Hospital, Bursa, Turkey

    Fatih Mehmet Celayir

  7. Department of Medical Genetics, Mustafa Kemal University, Hatay, Turkey

    Ozgur Aldemir

  8. Department of Medical Genetics, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey

    Mustafa Özen

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  1. Kemal Murat Canturk
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  2. Muhsin Ozdemir
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Correspondence to Kemal Murat Canturk.

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Canturk, K.M., Ozdemir, M., Can, C. et al. Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools. Mol Biol Rep 41, 8127–8135 (2014). https://doi.org/10.1007/s11033-014-3713-5

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  • DOI: https://doi.org/10.1007/s11033-014-3713-5

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