Abstract
Aim: Uterine leiomyoma is the most common benign tumor of female genitalia, and the incidence is rising gradually. This study explores the mechanism of miR-29 and STAT3 signaling pathways on uterine leiomyoma.Methods: GSE64763 and GSE5244 datasets were downloaded. Enrichment analyses were performed in GSE64763. PPI network was constructed, and the significant module was identified. Uterine leiomyoma cell lines were divided into NC, miR-29 mimic, anti-NC, and miR-29 inhibitor groups. Plate clone formation and Transwell assays detected the proliferation, invasion, and migration of cells. The expression levels of STAT3, proliferation, EMT, invasion-associated proteins were determined by Western blotting.Results: Differently expressed genes were mainly enriched in positive regulation of cell migration and gene expression, cell proliferation. Through GSEA, JAK-STAT is a significantly correlated enrichment pathway. A Venn diagram was drawn to identify the common miRNA (miR-29-3p). miR-29 inhibitors promoted protein expression of STAT-3, Cyclin D1, and c-Myc compared with the anti-NC control (P < 0.01), and miR-29 inhibitors promoted cell proliferation in uterine leiomyoma cells (P < 0.05). Furthermore, miR-29 inhibitors promoted the protein expression of MMP-2 and MMP-9 (P < 0.01), and EMT promoting proteins N-cadherin, snail, vimentin, and Transwell assay showed that miR-29 inhibitors promoted cell migration in uterine leiomyoma (P < 0.01).Conclusions: High expression of miR-29 could inhibit cell proliferation, invasion, and metastasis in uterine leiomyoma, which might be related to the inhibition of the STAT3 signaling pathway, and could provide a novel target for the treatment of uterine leiomyoma.
Highlights
Uterine leiomyoma, composed of smooth muscle and connective tissue, is the most common benign tumor in women [1]
A total of 204 differentially expressed genes (DEGs) were found in uterine leiomyoma, among which 139 were up-regulated, and 65 were down-regulated
Using Molecular Complex Detection tool (MCODE), we found that Signal transducer and activator of transcription 3 (STAT3), VEGFA, CCND1, and other genes were the hub genes of uterine leiomyoma, proving that they might play a significant role in the pathogenesis and progression uterine leiomyoma (Figure 3B)
Summary
Uterine leiomyoma, composed of smooth muscle and connective tissue, is the most common benign tumor in women (aged 30 to 50 years) [1]. In China, the incidence rate of uterine fibroids is the latest national statistics. The incidence rate of uterine fibroids is 30%. It is ignored because the number of myomas is small, the volume is small, and there is no irregular menstruation or other symptoms. Hysteromyoma is common in women aged 30 ~ 50, rare under 30, and very rare under 20. The incidence of hysteromyoma is the highest in women aged 40 ~ 50, accounting for about 51.2 %~ 60.9% [2]
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