Rui BingJie, Rui GuangHai, Yang YanFeng
Department of Obstetrics and Gynecology, Fushun Central Hospital, Fushun, Liaoning, China.
Department of Gynecology, CHA University, Seongnam, Gyeonggi, Republic of Korea.
Front Genet. 2025 Jun 6;16:1588278. doi: 10.3389/fgene.2025.1588278. eCollection 2025.
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.
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 |log (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.
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 collagenⅢ (COL III), CollagenⅠ (COL I), and Matrix Metalloproteinase-9 (MMP9).
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.
盆腔器官脱垂（POP）是一种常见的妇科疾病，由盆腔支持组织合成与降解失衡引起。影响细胞外基质（ECM）重塑的关键分子改变和基因突变与该病的发生有关。本研究旨在分析绝经后女性子宫骶韧带组织中的编码和非编码RNA（ncRNA），以阐明POP的分子机制。
我们纳入了5例POP患者和3例正常对照。收集子宫骶韧带组织样本，采用高通量转录组测序分析信使RNA（mRNA）、微小RNA（miRNA）、环状RNA（circRNA）和长链非编码RNA（lncRNA）。使用|log（倍数变化）|>1和校正P值（padj）<0.05的标准确定差异表达。进行生物信息学分析，包括基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，以评估差异表达基因的功能作用。构建竞争性内源RNA（ceRNA）网络，以探索lncRNA、miRNA和mRNA之间的相互作用。实时定量聚合酶链反应（qPCR）验证选定的靶点。
我们在POP组织中鉴定出60种mRNA、146种miRNA、29种lncRNA和176种circRNA具有显著差异表达。功能富集分析表明，这些转录本主要参与细胞衰老、炎症、ECM调节和细胞骨架组织。富集了几种信号通路，包括由丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶1/2（Erk1/2）、Ras相关蛋白（Rap1）、叉头框O（FOXO）和其他癌基因同源物介导的信号通路。ceRNA网络分析揭示了lncRNA、miRNA和mRNA之间的相互作用。值得注意的是，lncRNA FLJ20021在POP组织中显著下调，并与Ⅲ型胶原（COL III）、Ⅰ型胶原（COL I）和基质金属蛋白酶-9（MMP9）的表达改变相关。
我们的研究结果表明，POP组织中编码和ncRNA表达均有显著改变，提示多种途径失调导致其发病机制。特别是，ECM重塑和FLJ20021表达降低可能在组织退变中起关键作用，为未来的治疗干预提供了潜在靶点。
