Exploring biomarkers in the overactive bladder: Alterations in miRNA levels of a panel of genes in patients with OAB

Fırat, Elif; Aybek, Zafer; Akgün, Şakir; Küçüker, Kürşat; Akça, Hakan; Aybek, Hülya

doi:10.1002/nau.24065

Cited by 11 publications

(8 citation statements)

References 30 publications

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“…Contrary to expectations, patients showed lower GEF levels than controls, but the difference was not significant. Similar to this finding, in our previous study, the expression of miR-92a-3p, which is thought to inhibit GEF synthesis by targeting the gene responsible for GEF, was elevated in patients with OAB [14]. This observation supports the finding of lower GEF levels in OAB patients, and these data suggest that different factors may affect the regulation of ROCK2 in the detrusor muscle contraction mechanism in OAB.…”

Section: Discussionsupporting

confidence: 90%

“…Elevated levels of ROCK2, which functions in the cholinergic pathway, may result in OAB symptoms as a result of increased contraction via increased ROCK2 activation in the bladder smooth muscle. In support of this finding, in our previous study, the expression of miR-139-5p, which is thought to inhibit ROCK2 synthesis by targeting the gene responsible for ROCK2, was found to decrease in patients with OAB [14]. In the current study, ROCK2 was also seen to have a significant potential relationship in the ROC curves (AUC = 0.651).…”

Section: Discussionsupporting

confidence: 84%

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ADRB3, ROCK2, and GEF Levels in Overactive Bladder Patients

Fırat

Aybek

2022

Int Neurourol J

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Purpose: The aim of this study was to evaluate changes in levels of adrenergic receptor β3 (ADRB3), Rho-related kinase 2 (ROCK2), and guanine nucleotide exchange factor (GEF), which play key roles in the adrenergic and cholinergic pathways of contraction-relaxation harmony in voiding physiology, and to explore the relationship between these proteins and overactive bladder (OAB).Methods: This study included 60 idiopathic OAB patients and a healthy control group. A validated OAB-validated 8 questionnaire was completed by all participants. Serum levels of ADRB3, ROCK2, and GEF were examined with enzyme-linked immunosorbent assays. Patient and control groups were compared in terms of these levels, and receiver operating characteristic (ROC) curves were generated for all parameters.Results: The levels of ROCK2 were significantly elevated, but there were no correlations between the OAB symptom score and the serum levels of ROCK2, ADRB3, and GEF in OAB patients. In the ROC analysis, ROCK2 alone provided the strongest potential relationship (area under the curve=0.651) with 84.9% sensitivity. The ROCK2+GEF combination provided a satisfactory relationship (AUC=0.755). The AUC for the ADRB3+ROCK2+GEF combination was 0.752, with 64.2% sensitivity and 88.2% specificity.Conclusions: The study results suggest that alterations in serum ROCK2 levels and the use of this parameter in combination with ADRB3 and GEF levels can shed light on the pathophysiology of idiopathic OAB syndrome and provide a new perspective for treatment.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 84%

ADRB3, ROCK2, and GEF Levels in Overactive Bladder Patients

Fırat

Aybek

2022

Int Neurourol J

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“…MicroRNAs are short, approximately 22 nucleotide long noncoding RNA molecules that can post-transcriptionally regulate gene expression. Various microRNAs can serve as biomarkers of different lower urinary tract diseases, such as bladder cancer [ 139 ], bladder outlet obstruction [ 140 ], overactive bladder [ 141 ], and IC/BPS [ 142 , 143 ], and they have also been recognized as emerging therapeutic targets. In the present review, we identified two studies trialing microRNAs as potential drug targets in animal models of IC/BPS.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

et al. 2021

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present review provides an extensive overview of therapeutic approaches used in in vitro, ex vivo, and in vivo experimental models of IC/BPS. Publications were identified by electronic search of three online databases. Data were extracted for study design, type of treatment, main findings, and outcome, as well as for methodological quality and the reporting of measures to avoid bias. A total of 100 full-text articles were included. The majority of identified articles evaluated therapeutic agents currently recommended to treat IC/BPS by the American Urological Association guidelines (21%) and therapeutic agents currently approved to treat other diseases (11%). More recently published articles assessed therapeutic approaches using stem cells (11%) and plant-derived agents (10%), while novel potential drug targets identified were proteinase-activated (6%) and purinergic (4%) receptors, transient receptor potential channels (3%), microRNAs (2%), and activation of the cannabinoid system (7%). Our results show that the reported methodological quality of animal studies could be substantially improved, and measures to avoid bias should be more consistently reported in order to increase the value of preclinical research in IC/BPS for potential translation to a clinical setting.

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“…These results were confirmed by the qRT-PCR findings. Recently, Fırat et al also reported that miR-139-5p was significantly downregulated in OAB patient plasma (7). Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) was identified as a direct target of miR-139-5p and was effective in the ROCK2/myosin-light chain (MLC) and cholinergic pathway.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the combination of upregulated miR-98-5p and downregulated miR-139-5p in the plasm of patients' overactive bladder (OAB) was found to be a useful biomarker for OAB. However, no correlation was determined between the levels of miRs and OAB symptom score (7). Meanwhile, the above research only concentrated on finding the expression patterns of miRNA particularly in OAB patients.…”

Section: Original Articlementioning

confidence: 99%

MicroRNA expression profile in the spinal cord injured rat neurogenic bladder by next-generation sequencing

Shang¹,

Ou²,

Xu³

et al. 2020

Transl Androl Urol

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Background: An increasing amount of evidence has indicated that microRNAs (miRs) are involved in most biological conditions, including the neurogenic bladder (NB). However, to our knowledge, no studies have investigated these miR expressions in spinal cord-injured (SCI) rat NB. The goal of the study was to explore the miR expression profile in the SCI rat NB by next-generation sequencing (NGS).Methods: Female Wistar rats underwent spinal cord transection at T9-10 and were randomly divided into the SCI-1, SCI-2 and SCI-3 groups (n=5 for each group) whose bladder tissues were collected 1, 2, and 4 weeks after transection, respectively. The normal rats were used as the normal control (NC) group.MiRs microarray assays were used to detect the differentially expressed miRs between the groups by NGS, which was then verified by quantitative real-time polymerase chain reaction (qRT-PCR). Those significantly differently expressed miRs were analyzed with Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes bioinformatical analyses.Results: Compared with the NC group, 96, 28 and 51 miRs were downregulated in the rats' bladder in the SCI-1, SCI-2, and SCI-3 groups, respectively, and 133, 49, and 76 miRs were upregulated respectively. Specifically, miR-21-5p was the most significantly upregulated miR in all SCI groups. Also, 121 miRs (SCI-1 vs. SCI-2), 98 miRs (SCI-1 vs. SCI-3), and 26 miRs (SCI-2 vs. SCI-3) were of significantly different expression. Furthermore, a large set of genes implicated in essential signaling pathways were targeted by these miRs, including PI3K-Akt, MAPK, Rap1, and cGMP-PKG signaling pathways, along with the tight junction and metabolic pathways.Conclusions: This is the first demonstration of differentially expressed miRs, which may potentially serve as new molecular targets in the SCI rat NB.

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Exploring biomarkers in the overactive bladder: Alterations in miRNA levels of a panel of genes in patients with OAB

Cited by 11 publications

References 30 publications

ADRB3, ROCK2, and GEF Levels in Overactive Bladder Patients

ADRB3, ROCK2, and GEF Levels in Overactive Bladder Patients

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

MicroRNA expression profile in the spinal cord injured rat neurogenic bladder by next-generation sequencing

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