Umbilical cord mesenchymal stem cells (UCMSCs) are regarded as an ideal source for clinical use. Increasing evidence has suggested that microRNAs (miRNAs) work as a crucial regulator in the development of plentiful diseases, including intrauterine adhesions (IUA). Herein, we investigated the specific impacts of UCMSCs overexpressing miR-455-5p in IUA. UCMSCs were cocultured with endometrial stromal cells (ESCs). Thirty-two female mice were divided into four different treated groups: sham, model, model + UCMSC-miR-NC and model + UCMSC-miR-455-5p. Mice in model groups were induced by uterine curettage. MiR-455-5p overexpressed UCMSCs facilitated the proliferation and cell cycle progression of ESCs according to 5-ethynyl-2′-deoxyuridine assay and flow cytometry analysis. Hematoxylin-eosin and Masson staining revealed that miR-455-5p upregulation in UCMSCs increased the number of endometrial glands and suppressed endometrial fibrosis in murine uterine tissues. Western blotting displayed that miR-455-5p overexpressed UCMSCs promoted the activation of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling in ESCs and murine uterine tissues. Mechanistically, miR-455-5p targeted 3’ untranslated region of suppressor of cytokine signaling 3 (SOCS3), which was confirmed by luciferase reporter assay. Reverse transcription quantitative polymerase chain reaction demonstrated that miR-455-5p was lowly expressed and SOCS3 was highly expressed in murine uterine tissues of IUA model. Moreover, Pearson correlation analysis showed that their expression was inversely correlated. Rescue assays suggested that inhibiting JAK/STAT3 signaling reversed effects of miR-455-5p on the behaviors of ESCs. The results indicated that miR-455-5p overexpression in UCMSCs helps to attenuate endometrial injury and repair damaged endometrium by activating SOCS3-mediated JAK/STAT3 signaling.

Intrauterine adhesion (IUA) is the clinical manifestation of endometrial fibrosis. The dysregulation of microRNAs (miRNAs) has been confirmed to implicate in a diversity of human diseases, including IUA. Nevertheless, the specific function of miR-223-3p in IUA remains to be clarified. Reverse transcription quantitative polymerase chain reaction analysis displayed the downregulation of miR-223-3p in IUA tissues and endometrial epithelial cells (EECs). Results from wound healing assay, Transwell assay and western blotting showed that TGF-β facilitated the migration and invasion of EECs and induced epithelial-mesenchymal transition (EMT) process as well as extracellular matrix (ECM) deposition. Overexpression of miR-223-3p in EECs was shown to suppress the effects induced by TGF-β. Bioinformatics analysis and luciferase reporter assay revealed the binding relation between miR-223-3p and SP3. SP3 was highly expressed in IUA and its expression was inversely correlated with miR-223-3p expression in IUA tissue samples. Additionally, upregulation of SP3 reversed the influence of miR-223-3p on the phenotypes of EECs. In conclusion, miR-223-3p alleviates TGF-β-induced cell migration, invasion, EMT process and ECM deposition in EECs by targeting SP3.