Abstract
Background
Pelvic organ prolapse (POP) is a prevalent gynecological disorder, characterized by anomalies in the function or position of the pelvic organs, frequently manifesting as prolapse of the uterus and both the anterior and posterior vaginal walls. POP is primarily linked to damage to both the pelvic floor muscles and connective tissue, with the majority of molecules and genetic mutations associated with POP pertaining to the synthesis and degradation of pelvic support tissues. Recently, the significant role of non-coding RNA (ncRNA) in epigenetic regulation has garnered extensive attention. However, the functions of various RNAs including microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and messenger RNA (mRNA) in the pathogenesis of POP remain elusive.
Results
This study collected uterosacral ligament tissue from five POP patients and three age-matched controls for Illumina PE150 sequencing, identifying 60 mRNAs, 176 miRNAs, 29 lncRNAs, and 176 circRNAs with statistically significant differences in abundance between the POP and control groups. The accuracy of the high-throughput next-generation sequencing results was further validated through qRT-PCR analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that differentially expressed genes were predominantly involved in the MAPK, Erk1/2, rap1, FOXO, and ErbB signaling pathways. KEGG disease analysis indicated that these genes are closely associated with inflammation, adhesion plaques, cellular aging, apoptosis, and the cytoskeleton. Utilizing the competitive endogenous RNA (ceRNA) regulatory mechanism, we constructed a lncRNA/circRNA-miRNA-mRNA network. Finally, from the RNAs identified in the high-throughput whole transcriptome sequencing, we randomly selected ENSG00000254531 and confirmed that this molecule influences fibroblast proliferative capacity.
Conclusion
Our comprehensive transcriptome study reveals the gene expression characteristics in the uterosacral ligament tissues of postmenopausal women with POP. This study provides essential data support for identifying key mRNAs and non-coding RNAs associated with the potential molecular mechanisms of POP. We screened differentially expressed miRNAs, lncRNAs, circRNAs, and mRNAs, evaluated their functional enrichments, and constructed ceRNA network to elucidate potential regulatory mechanisms and their corresponding functions. Finally, we validated the differential expression of a critical lncRNA in tissues and cells through in vitro experiments. Our findings demonstrate that the dysregulated lncRNA significantly impacts fibroblast proliferation. The identification of key lncRNAs in our study provides valuable insights into POP-related lncRNAs and may serve as important factors in the diagnosis and treatment of pop. This research introduces new candidate markers for exploring the pathogenesis of pelvic organ prolapse.