microRNA-145-3p/CTNND1/FGF18 Signaling Pathway Regulates Apoptosis and Extracellular Matrix Degradation in the Vaginal Wall Fibroblasts of Patients with Pelvic Organ Prolapse.

SETTING: This study was conducted at both clinical and cellular levels, utilizing patient-derived vaginal wall tissues and cultured vaginal wall fibroblasts (VWFs). PARTICIPANTS: The study participants were patients diagnosed with Pelvic Organ Prolapse (POP), from whom vaginal wall tissues and fibroblasts (VWFs) were obtained. OBJECTIVES: The primary objective of this study was to clarify the precise function and molecular mechanism of microRNA-145-3p in the pathogenesis of POP, focusing on its impact on apoptosis and extracellular matrix (ECM) degradation. METHODS: Validation and Analysis: microRNA-145-3p expression was validated using qRT-PCR. Functional effects on proliferation, apoptosis, migration, and invasion were assessed via CCK8, flow cytometry, and Transwell assays. Pathway and Protein Assessment: Western Blotting was employed to evaluate ECM-related proteins, Wnt/β-catenin pathway-related and PI3K/AKT pathway-related proteins. Target Identification: Bioinformatics prediction, dual-luciferase reporter gene assays, and CHIP were utilized to confirm the targeting relationship between microRNA-145-3p and CTNND1. DESIGN: This was an experimental study integrating clinical tissue analysis, in vitro cell culture models, and molecular biology techniques to establish a functional and mechanistic pathway. RESULTS: microRNA-145-3p was significantly elevated in the VWFs of POP patients. This elevated expression correlated with heightened apoptosis and ECM degradation. CTNND1 was identified as a direct target of microRNA-145-3p. Targeting CTNND1 led to the suppression of the Wnt/β-catenin signaling pathway and a subsequent decrease in FGF18 expression. CONCLUSIONS: In POP, the molecular mechanism involves microRNA-145-3p targeting CTNND1, which suppresses the Wnt/β-catenin signaling pathway, alters FGF18 expression, and consequently enhances apoptosis and ECM metabolism in vaginal wall fibroblasts, contributing to tissue weakness. LIMITATIONS: The provided text does not explicitly state the limitations of this study. Potential limitations could include the sample size of the patient cohort, the need for further in vivo validation, and the exploration of additional downstream targets or interacting pathways.