Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction.

Hashemi Gheinani, Ali; Kiss, Bernhard; Moltzahn, Felix Roman; Keller, Irene; Bruggmann, Rémy; Rehrauer, Hubert; Fournier, Catharine Aquino; Burkhard, Fiona C.; Monastyrskaya-Stäuber, Katia (2017). Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction. JCI insight, 2(2), e89560. JCI Insight 10.1172/jci.insight.89560

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Hashemi Gheinani, Ali; Kiss, Bernhard; Moltzahn, Felix Roman; Burkhard, Fiona C. and Monastyrskaya-Stäuber, Katia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2379-3708

Publisher:

JCI Insight

Language:

English

Submitter:

Katharina Morgenegg

Date Deposited:

05 Mar 2018 12:29

Last Modified:

11 Mar 2018 02:12

Publisher DOI:

10.1172/jci.insight.89560

PubMed ID:

28138557

BORIS DOI:

10.7892/boris.96882

URI:

https://boris.unibe.ch/id/eprint/96882

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