title: Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction.
abstract: Bladder outlet obstruction (BOO) induces significant organ remodeling, leading to lower urinary tract symptoms accompanied by urodynamic changes in bladder function. Here, we report mRNA and miRNA transcriptome sequencing of bladder samples from human patients with different urodynamically defined states of BOO. Patients' miRNA and mRNA expression profiles correlated with urodynamic findings. Validation of RNA sequencing results in an independent patient cohort identified combinations of 3 mRNAs (NRXN3, BMP7, UPK1A) and 3 miRNAs (miR-103a-3p, miR-10a-5p, miR-199a-3p) sufficient to discriminate between bladder functional states. All BOO patients shared cytokine and immune response pathways, TGF-β and NO signaling pathways, and hypertrophic PI3K/AKT signaling pathways. AP-1 and NFkB were dominant transcription factors, and TNF-α was the top upstream regulator. Integrated miRNA-mRNA expression analysis identified pathways and molecules targeted by differentially expressed miRNAs. Molecular changes in BOO suggest an increasing involvement of miRNAs in the control of bladder function from the overactive to underactive/acontractile states.
authors.affiliation: Urology Research Laboratory, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Ali Hashemi
authors.initials: AH
authors.lastname: Gheinani
authors.affiliation: Department of Urology, University Hospital, Bern, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kiss
authors.affiliation: Department of Urology, University Hospital, Bern, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Moltzahn
authors.affiliation: Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Keller
authors.affiliation: Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bruggmann
authors.affiliation: Functional Genomics Center Zurich, Zurich, Switzerland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Rehrauer
authors.affiliation: Functional Genomics Center Zurich, Zurich, Switzerland.
authors.forename: Catharine Aquino
authors.initials: CA
authors.lastname: Fournier
authors.affiliation: Department of Urology, University Hospital, Bern, Switzerland.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Burkhard
authors.affiliation: Urology Research Laboratory, Department of Clinical Research, University of Bern, Bern, Switzerland.|Department of Urology, University Hospital, Bern, Switzerland.
authors.forename: Katia
authors.initials: K
authors.lastname: Monastyrskaya
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D001748:Urinary Bladder Neck Obstruction / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000077295:Urinary Bladder, Underactive / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D014563:Urodynamics; D060167:Uroplakin Ia / Q000235:genetics
chemical_list: C525819:BMP7 protein, human; D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7; D016207:Cytokines; C547183:MIRN10 microRNA, human; C544749:MIRN103 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; C086451:UPK1A protein, human; D060167:Uroplakin Ia; C531408:mirn199 microRNA, human; C082354:neurexin IIIalpha; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt