Objective: The aims of this study were to investigate microRNA (miRNA) expression profiles in the periurethral vaginal wall tissues of postmenopausal women with and without stress urinary incontinence (SUI) and to explore the putative target genes associated with SUI via miRNA-messenger RNA (mRNA) pair prediction.
Methods: Periurethral vaginal wall tissues of postmenopausal women with SUI (n = 13) and matched continent postmenopausal women (n = 13) were collected during transvaginal surgical operation. Total RNAs were extracted and miRNAs were profiled by TaqMan Array Human MicroRNA assays in three case-control pairs. TargetScanS, PicTar, and miRanda were used to obtain the putative miRNA-mRNA pairs based on sequence data, and three pairs were predicated. The relative expression levels of miRNAs in predicated miRNA-mRNA pairs were quantified in 10 other case-control pairs by real-time polymerase chain reaction. The expression levels of mRNAs and corresponding proteins were estimated via real-time polymerase chain reaction and Western blot analysis.
Results: Twelve miRNAs were identified to be differentially expressed between two groups: the significantly up-regulated let-7a, miR-101#, miR-125b-2#, miR-190b, and miR-892b, and the down-regulated miR-124, miR-330-3p, miR-485-3p, miR-517b, miR-523, miR-589, and miR-93#. Moreover, three miRNA-mRNA pairs of interest were established via computational algorithms: miR-124 and growth factor receptor-bound protein 2; miR-330-3p and bicaudal D homolog 2; and miR-93# and signal transducer and activator of transcription 3. The expression levels of the three miRNAs were quantified, and a reduction in SUI was revealed. On the other hand, increased expression levels of predicated mRNAs and their protein products were detected.
Conclusions: This study reports the differential expression of 12 miRNAs in SUI and predicates three miRNA-mRNA pairs. Interestingly, all three predicated target genes are associated with neurodegenerative conditions, indicating the potential significance of neurodegenerative mechanisms in the etiology of SUI.
(C) 2014 by The North American Menopause Society.