ORIGINAL RESEARCH article
Front. Genet.
Sec. RNA
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1588278
This article is part of the Research TopicCurrent Advances in the Understanding and Management of Pelvic Organ ProlapseView all 6 articles
Unveiling pathogenesis of pelvic organ prolapse through transcriptomic and bioinformatic analyses in uterosacral ligament tissues of postmenopausal women
Provisionally accepted
- 1Fushun Central Hospital, Fushun, Liaoning, China
- 2CHA University, Seongnam, Gyeonggi, Republic of Korea
- 3Fushun maternal and child health hospital, Fushun, China
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Background: Pelvic organ prolapse (POP) is a common gynecological disorder arising from an imbalance in the synthesis and degradation of pelvic supportive tissues. Alterations in key molecules and genetic mutations affecting extracellular matrix (ECM) remodeling have been implicated in its development. This study aimed to profile coding and noncoding RNAs(ncRNAs) in uterosacral ligament tissues of postmenopausal women to elucidate POP's molecular mechanisms. Methods: We enrolled five POP patients and three normal controls. Uterosacral ligament tissue samples were collected and analyzed using high-throughput transcriptome sequencing to profile messenger RNAs (mRNAs), micro RNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs). Differential expression was determined using the criteria of |log₂(fold change)|＞1 and an adjusted p-value (padj) ＜ 0.05. Bioinformatics analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, were performed to assess the functional roles of the differentially expressed genes. Competing endogenous RNA (ceRNA) networks were constructed to explore interactions among lncRNAs, miRNAs, and mRNAs. Real-time quantitative polymerase chain reaction (qPCR) validated selected targets. Results: We identified 60 mRNAs, 146 miRNAs, 29 lncRNAs, and 176 circRNAs with significant differential expression in POP tissues. Functional enrichment analyses revealed that these transcripts are primarily involved in cellular senescence, inflammation, ECM regulation, and cytoskeletal organization. Several signaling pathways were enriched, including those mediated by mitogen-activated protein kinase (MAPK), Extracellular Signal-Regulated Kinase 1/2(Erk1/2), Ras-related proteins (Rap1), Forkhead Box O (FOXO), and other oncogene homologs. Analysis of ceRNA networks uncovered interactions among lncRNAs, miRNAs, and mRNAs. Notably, lncRNA FLJ20021 was significantly downregulated in POP tissues and correlated with altered expression of collagen Ⅲ (COL III), Collagen Ⅰ (COL I), and Matrix Metalloproteinase-9(MMP9). Conclusions: Our findings demonstrate significant alterations in both coding and ncRNAs expression in POP tissues, suggesting that dysregulation of multiple pathways contributes to its pathogenesis. In particular, ECM remodeling and reduced FLJ20021 expression may play key roles in tissue degeneration, offering potential targets for future therapeutic intervention.
Keywords: Pelvic Organ Prolapse, Uterosacral ligament, non-coding RNA, Transcriptome sequencing, FLJ20021
Received: 06 Mar 2025; Accepted: 22 May 2025.
Copyright: © 2025 Rui, Rui and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: YanFeng Yang, Fushun maternal and child health hospital, Fushun, China
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