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Two microRNA clusters may determine the biological functions of microRNA-regulated pathways in underactive bladder
32nd Annual EAU Congress, 24-28 March 2017, London, United Kingdom
115
Two microRNA clusters may determine the biological functions of microRNA-regulated pathways in underactive bladder Eur Urol Suppl 2017; 16(3);e187
Hashemi Gheinani A.1, Burkhard F.2, Monastyrskaya K.2 1
Urology Research Laboratory, Dept. of Clinical Research, Bern, Switzerland, 2University Hospital Bern, Dept. of Urology, Bern, Switzerland INTRODUCTION & OBJECTIVES: MicroRNAs regulate diverse biological processes. Previously we identified miRNA-regulated pathways in bladder outlet obstruction (BOO)-induced bladder dysfunction. MiRNAs in a cluster reside in genomic proximity (<10 kb), and miRNA families have seed sequence homology. Expression of miRNA cluster might be mediated by common transcription factors, and clustered miRNAs often regulate same biological processes. Here we probed functional associations of BOO phenotype-specific miRNAs and identified several co-expressed miRNA sub-networks. MATERIAL & METHODS: MiRNA sequences and genomic coordinates were extracted from miRBase version 21. Large scale chromosomal mapping of human miRNA structural clusters was done using MIReStruC-1.0 package. Next-generation sequencing datasets of patients’ biopsies with urodynamically established BOO with and without detrusor overactivity (DO and BO groups, respectively) or with detrusor underactivity (UA group) were used to perform miRNA-mRNA integrated analysis and target pairing. We included the miRNA families extracted from miRBase version 21. Sequences were aligned with MAFFT version 7 and Clustal X 2.1 and manually refined with RALEE — RNA version 0.8. RESULTS: In DO group hsa-miR-376c-3p/hsa-miR-409-3p cluster was identified on chromosome 14. In BO group hsa-miR-889-3p/hsa-miR-410-3p/hsa-miR-409-3p cluster was detected on chromosome 14. Three miRNA clusters were detected in UA group: hsa-miR-25-3p/hsa-miR-106b-3p cluster on chromosome 7 and 2 clusters on chromosome 1: hsa-miR-199a-3p/hsa-miR-3120-3p cluster and hsamiR-429/hsa-miR-200b-3p cluster belonging to miR-200bc/429/548a family. All clustered miRNAs were intergenic. Integrated miRNA-mRNA expression profiling in all miRNA clusters revealed no significant target overlap, 90% of targets of up-regulated miRNA clusters were also up-regulated. In DO and BO groups no major contribution of the miRNA clusters to the biological functions of miRNA-regulated pathways was detected. In contrast, in UA group 2 down-regulated miRNA clusters were necessary and sufficient to determine the functions of all miRNA-regulated pathways. The appropriately regulated targets of hsa-miR-199a-3p/hsa-miR-3120-3p and hsa-miR-429/hsa-miR-200b-3p clusters constituted the majority of miRNA-regulated pathway elements in the UA state. CONCLUSIONS: Multiple co-expressed miRNAs may cooperatively influence biological processes and the acontractile urodynamic phenotype in the underactive bladder. Elucidating the down-regulation mechanisms of these miRNA clusters may help determine the “point of no return” for the loss of bladder function during BOO.
Eur Urol Suppl 2017; 16(3);e187 Powered by TCPDF (www.tcpdf.org)
115
Two microRNA clusters may determine the biological functions of microRNA-regulated pathways in underactive bladder Eur Urol Suppl 2017; 16(3);e187
Hashemi Gheinani A.1, Burkhard F.2, Monastyrskaya K.2 1
Urology Research Laboratory, Dept. of Clinical Research, Bern, Switzerland, 2University Hospital Bern, Dept. of Urology, Bern, Switzerland INTRODUCTION & OBJECTIVES: MicroRNAs regulate diverse biological processes. Previously we identified miRNA-regulated pathways in bladder outlet obstruction (BOO)-induced bladder dysfunction. MiRNAs in a cluster reside in genomic proximity (<10 kb), and miRNA families have seed sequence homology. Expression of miRNA cluster might be mediated by common transcription factors, and clustered miRNAs often regulate same biological processes. Here we probed functional associations of BOO phenotype-specific miRNAs and identified several co-expressed miRNA sub-networks. MATERIAL & METHODS: MiRNA sequences and genomic coordinates were extracted from miRBase version 21. Large scale chromosomal mapping of human miRNA structural clusters was done using MIReStruC-1.0 package. Next-generation sequencing datasets of patients’ biopsies with urodynamically established BOO with and without detrusor overactivity (DO and BO groups, respectively) or with detrusor underactivity (UA group) were used to perform miRNA-mRNA integrated analysis and target pairing. We included the miRNA families extracted from miRBase version 21. Sequences were aligned with MAFFT version 7 and Clustal X 2.1 and manually refined with RALEE — RNA version 0.8. RESULTS: In DO group hsa-miR-376c-3p/hsa-miR-409-3p cluster was identified on chromosome 14. In BO group hsa-miR-889-3p/hsa-miR-410-3p/hsa-miR-409-3p cluster was detected on chromosome 14. Three miRNA clusters were detected in UA group: hsa-miR-25-3p/hsa-miR-106b-3p cluster on chromosome 7 and 2 clusters on chromosome 1: hsa-miR-199a-3p/hsa-miR-3120-3p cluster and hsamiR-429/hsa-miR-200b-3p cluster belonging to miR-200bc/429/548a family. All clustered miRNAs were intergenic. Integrated miRNA-mRNA expression profiling in all miRNA clusters revealed no significant target overlap, 90% of targets of up-regulated miRNA clusters were also up-regulated. In DO and BO groups no major contribution of the miRNA clusters to the biological functions of miRNA-regulated pathways was detected. In contrast, in UA group 2 down-regulated miRNA clusters were necessary and sufficient to determine the functions of all miRNA-regulated pathways. The appropriately regulated targets of hsa-miR-199a-3p/hsa-miR-3120-3p and hsa-miR-429/hsa-miR-200b-3p clusters constituted the majority of miRNA-regulated pathway elements in the UA state. CONCLUSIONS: Multiple co-expressed miRNAs may cooperatively influence biological processes and the acontractile urodynamic phenotype in the underactive bladder. Elucidating the down-regulation mechanisms of these miRNA clusters may help determine the “point of no return” for the loss of bladder function during BOO.
Eur Urol Suppl 2017; 16(3);e187 Powered by TCPDF (www.tcpdf.org)