Analysis of key genes and micro-RNA-mRNA regulatory networks in women with ulcerative interstitial cystitis/pain bladder syndrome.

Introduction And Hypothesis: This aim of this study was to better understand ulcerative interstitial cystitis/painful bladder syndrome (IC/PBS) at the molecular level and provide new clues related to diagnosis and treatment.

Methods: The microarray data set GSE11783, including the mRNA and miRNA profiles of bladder tissue obtained at cystoscopic biopsy from patients with ulcerative IC/PBS (presence of at least one Hunner's ulcer) and normal controls, was downloaded from the GEO (Gene Expression Omnibus) database (National Center for Biotechnology Information). These were evaluated using Greenspring GX and Ingenuity Pathway Analysis (IPA) software. The differentially expressed genes (DEGs) and miRNAs (DEMs) in these two groups were identified. Subsequently, the DEGs were subjected to functional analysis, and a protein-protein interaction (PPI) network was constructed. Finally, the miRNA-mRNA regulatory network was visualized using Cystoscope software.

Results: Four DEMs and 1521 DEGs were identified between the ulcerative IC/PBS and control groups. The PPI network of the DEGs was constructed by STRING, which was composed of 393 nodes and 1039 edges, including 221 upregulated genes and 172 downregulated genes. Moreover, 27 genes in the PPI network were identified as hub genes in the IC/PBS group, e.g., PNOC, SSTR1, FPR3, GPR18 and APLNR. Subsequently, 27 clusters were selected from the PPI network using MCODE. It was shown that the most significant cluster consisted of 22 nodes and 231 edges. Moreover, miR-21 was the most significantly upregulated miRNA and was predicted to target one upregulated gene (RASGRP1) and two downregulated genes (KLF5 and SC5D).

Conclusions: The results of this data mining and integration provide further information on the possible molecular basis of IC/PBS pathogenesis as well as potential biomarkers and therapeutic targets for ulcerative IC/PBS diagnosis and treatment.