Research Paper Volume 14, Issue 3 pp 1307—1320
Inhibiting effect of miR-29 on proliferation and migration of uterine leiomyoma via the STAT3 signaling pathway
- 1 Department of Medical Imaging and Department of Ultrasound, Hebei Medical University and Hebei General Hospital, Shijiazhuang 050051, Hebei, China
- 2 Department of Ultrasound, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
- 3 Department of Second Division of Geriatrics, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
- 4 Department of Medical Examination Center, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
- 5 Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
- 6 Ultrasound Department, Hebei Medical University and Hebei General Hospital, Shijiazhuang 050051, Hebei, China
Received: August 4, 2021 Accepted: January 11, 2022 Published: February 2, 2022
https://doi.org/10.18632/aging.203873How to Cite
Copyright: © 2022 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
(STAT3): Signal transducer and activator of transcription 3; (PPI): protein-protein interaction; (NC): negative control; (GSEA): Gene Set Enrichment Analysis; (MMP2/9): matrix metalloproteinase 2/9; (GEO): Gene Expression Omnibus; (PCA): principal component analysis; (DEGs): differentially expressed genes; GO: (Gene Ontology); (KEGG): Kyoto Encyclopedia of Genes and Genomes; (BP): biological processes; (STRING): Search Tool for the Retrieval of Interacting Genes; (MCODE): Molecular Complex Detection tool; (PBS): phosphate-buffered saline; (RIPA): ristocetin-induced platelet agglutination; (SDS-PAGE): sodium dodecyl sulfate-polyacrylamide gel electrophoresis; (PVDF): Polyvinylidene Fluoride; (UtLMCs): uterine leiomyoma cells; (MMPs): matrix Metalloproteinases; (VEGF): vascular endothelial growth factor; (EMT): Epithelial-mesenchymal transformation..